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  31. <title>What Exactly Is HLA &#8220;Matching&#8221;?</title>
  32. <link>https://cytologicsbio.com/what-exactly-is-hla-matching/</link>
  34. <dc:creator><![CDATA[Cytologics]]></dc:creator>
  35. <pubDate>Sun, 04 Feb 2024 18:01:55 +0000</pubDate>
  36. <category><![CDATA[Scientific Knowledge]]></category>
  37. <category><![CDATA[HLA System]]></category>
  38. <guid isPermaLink="false">https://cytologicsbio.com/?p=57241</guid>
  39.  
  40. <description><![CDATA[Overview HLA matching refers to the process of comparing the human leukocyte antigen (HLA) types of a donor and a [&#8230;]]]></description>
  41. <content:encoded><![CDATA[
  42. <h2 class="wp-block-heading"><strong>Overview</strong></h2>
  43.  
  44.  
  45.  
  46. <p style="font-size: 18px;">HLA matching refers to the process of comparing the human leukocyte antigen (HLA) types of a donor and a recipient to determine the degree of compatibility between them for organ and tissue transplantation.</p>
  47.  
  48.  
  49.  
  50. <p style="font-size: 18px;">HLA are proteins found on the surface of cells that help the immune system <a href="https://www.ncbi.nlm.nih.gov/books/NBK546662/" target="_blank" rel="noopener"><span class="has-inline-color has-vivid-cyan-blue-color"><span style="text-decoration: underline;">recognize &#8220;self&#8221; from &#8220;non-self.”</span></span></a><a href="#references"><sup>[1]</sup></a> HLA laboratories and clinicians determine histocompatibility between a patient and a donor by analyzing certain HLA genes, <a href="https://www.astctjournal.org/article/S1083-8791(08)00274-7/fulltext" target="_blank" rel="noopener"><span class="has-inline-color has-vivid-cyan-blue-color"><span style="text-decoration: underline;">usually the 6 antigens at the HLA-A, -B and -DRB1 loci.</span></span></a><a href="#references"><sup>[2]</sup></a> In general, the more of these HLA genes two people share in common, the better match they are for transplantation.</p>
  51.  
  52.  
  53.  
  54. <p style="font-size: 18px;">HLA matching is also important in cell and gene therapies, which involve the use of cells or genetic material to treat diseases. In these therapies, HLA matching is important to prevent immune rejection of the therapy and to ensure that the therapy is effective.</p>
  55.  
  56.  
  57.  
  58. <h2 class="wp-block-heading"><strong>Why is HLA “matching” important?</strong></h2>
  59.  
  60.  
  61.  
  62. <p style="font-size: 18px;">When a person receives an organ transplant or cell therapy, their immune system may recognize the donor tissue as foreign and attack it, leading to rejection or <a href="https://www.lls.org/treatment/types-treatment/stem-cell-transplantation/graft-versus-host-disease" target="_blank" rel="noopener"><span class="has-inline-color has-vivid-cyan-blue-color"><span style="text-decoration: underline;">graft-versus-host disease.</span></span></a><a href="#references"><sup>[3]</sup></a> HLA matching is important because the more closely matched the donor and recipient are in terms of their HLA types, the less likely the recipient&#8217;s immune system is to reject the transplant.</p>
  63.  
  64.  
  65.  
  66. <p style="font-size: 18px;">HLA matching is usually performed by analyzing the DNA of the donor and recipient to identify the HLA alleles they possess. A higher degree of HLA matching between the donor and recipient is associated with better transplant outcomes, including reduced risk of rejection and longer graft survival.</p>
  67.  
  68.  
  69.  
  70. <div class="wp-block-buttons is-content-justification-center is-layout-flex wp-block-buttons-is-layout-flex">
  71. <div class="wp-block-button"><a class="wp-block-button__link has-luminous-vivid-orange-background-color has-background" href="https://cytologicsbio.com/2021/01/31/how-to-decipher-human-leukocyte-antigen-hla-nomenclature/"><strong>Related: How to Decipher HLA Nomenclature</strong></a></div>
  72. </div>
  73.  
  74.  
  75.  
  76. <div class="wp-block-spacer" style="height: 20px;" aria-hidden="true"> </div>
  77.  
  78.  
  79.  
  80. <h2 class="wp-block-heading"><strong>How is HLA “matching” performed?</strong></h2>
  81.  
  82.  
  83.  
  84. <p style="font-size: 18px;">HLA matching is typically performed using molecular techniques that analyze the DNA of the donor and recipient to determine their HLA types. There are several methods used for HLA typing, including:</p>
  85.  
  86.  
  87.  
  88. <ul style="font-size: 18px;">
  89. <li style="font-size: 18px; line-height: 1.5; padding-bottom: 18px;"><strong>Polymerase chain reaction (PCR) sequencing</strong> – PCR is a technique that can amplify a specific segment of DNA, making it easier to analyze. PCR sequencing involves amplifying the DNA segments that encode for HLA molecules, and then sequencing these segments to identify the specific HLA alleles present in the sample.</li>
  90. <li style="font-size: 18px; line-height: 1.5; padding-bottom: 18px;"><strong>Sequence-specific oligonucleotide probes (SSOP)</strong> – This technique involves using short, synthetic DNA probes that are specific to known HLA alleles. These probes are labeled with a fluorescent or radioactive tag, and hybridize to the DNA of the donor and recipient, allowing identification of the HLA alleles present.</li>
  91. <li style="font-size: 18px; line-height: 1.5; padding-bottom: 18px;"><strong>Sequence-specific primers (SSP)</strong> – SSP is similar to SSOP, but instead of using probes, short DNA primers are used to amplify specific regions of the HLA genes. The amplified DNA is then analyzed to determine the specific HLA alleles present.</li>
  92. <li style="font-size: 18px; line-height: 1.5; padding-bottom: 18px;"><strong>Next-generation sequencing (NGS)</strong> – NGS is a newer technique that allows for high-throughput sequencing of DNA samples. NGS can be used to sequence the entire HLA region, providing a detailed profile of the HLA alleles present in the donor and recipient.</li>
  93. </ul>
  94.  
  95.  
  96.  
  97. <p style="font-size: 18px;">After the HLA typing is performed, the donor and recipient&#8217;s HLA types are compared to determine the degree of compatibility between them. The <a href="https://www.researchgate.net/publication/23188666_National_Marrow_Donor_Program_HLA_Matching_Guidelines_for_Unrelated_Adult_Donor_Hematopoietic_Cell_Transplants" target="_blank" rel="noopener"><span class="has-inline-color has-vivid-cyan-blue-color"><span style="text-decoration: underline;">National Marrow Donor Program guidelines</span></span></a> define a minimum acceptable level of matching as 5 of 6 allele matching for HLA-A, -B, and -DRB1 for unrelated donor transplant requests.<a href="#references"><sup>[4]</sup></a></p>
  98.  
  99.  
  100.  
  101. <h2 class="wp-block-heading"><strong>What are the risks and challenges of HLA &#8220;matching&#8221;?</strong></h2>
  102.  
  103.  
  104.  
  105. <p style="font-size: 18px;">HLA matching is an important aspect of tissue transplantation and cell therapies, but there are several risks and challenges associated with the process, including:</p>
  106.  
  107.  
  108.  
  109. <ul style="font-size: 18px;">
  110. <li style="font-size: 18px; line-height: 1.5; padding-bottom: 18px;">Risk of rejection: Even with good HLA matching, there is still a risk of rejection, as the immune system can still recognize the transplanted organ as foreign.</li>
  111. <li style="font-size: 18px; line-height: 1.5; padding-bottom: 18px;">Limited donor pool: Finding a suitable donor can be challenging because not all potential donors will be HLA-compatible with the recipient. The more stringent the matching requirements, the smaller the pool of potential donors.</li>
  112. <li style="font-size: 18px; line-height: 1.5; padding-bottom: 18px;">Time-consuming and expensive: HLA typing is a time-consuming and expensive process, which can make it challenging to perform for large numbers of potential donors or recipients.</li>
  113. <li style="font-size: 18px; line-height: 1.5; padding-bottom: 18px;">Complex HLA genetics: <a href="https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-1-8" target="_blank" rel="noopener"><span class="has-inline-color has-vivid-cyan-blue-color"><span style="text-decoration: underline;">HLA genes are highly polymorphic,</span></span></a> meaning that there are many different HLA alleles present in the human population.<a href="#references"><sup>[5]</sup></a> This can make it difficult to identify compatible donors, especially for patients who have rare HLA types.</li>
  114. <li style="font-size: 18px; line-height: 1.5; padding-bottom: 18px;">Need for immunosuppressive drugs: To prevent rejection, recipients of organ transplants typically need to take immunosuppressive drugs for the rest of their lives. These drugs can have significant side effects and increase the risk of infection and other complications.</li>
  115. </ul>
  116.  
  117.  
  118.  
  119. <h2 class="wp-block-heading"><strong>Conclusion</strong></h2>
  120.  
  121.  
  122.  
  123. <p style="font-size: 18px;">Overall, HLA matching is an important component of organ and tissue transplantation and cell therapies, but it is not without risks and challenges. Improvements in HLA typing technology and the development of new immunosuppressive drugs may help to overcome some of these challenges in the future.</p>
  124.  
  125.  
  126.  
  127. <p style="font-size: 18px;">At Cytologics, <a href="https://cytologicsbio.com/products/"><span class="has-inline-color has-vivid-cyan-blue-color"><span style="text-decoration: underline;">our product portfolio</span></span></a> includes immune cells with high resolution HLA-A, HLA-B and HLA-C typing. We understand that HLA information is vital to the outcomes of your experiments. <a href="https://cytologicsbio.com/contact/"><span class="has-inline-color has-vivid-cyan-blue-color"><span style="text-decoration: underline;">Contact us today</span></span></a> to discuss how we can support your research with HLA-typed immune cell products.</p>
  128.  
  129.  
  130.  
  131. <div class="wp-block-buttons is-content-justification-center is-layout-flex wp-block-buttons-is-layout-flex">
  132. <div class="wp-block-button"><a class="wp-block-button__link has-luminous-vivid-orange-background-color has-background" href="https://cytologicsbio.com/product/hla-typed-peripheral-blood-mononuclear-cells/"><strong>Request HLA-Typed PBMCs</strong>→</a></div>
  133. </div>
  134.  
  135.  
  136.  
  137. <div id="references" class="wp-block-ps2id-block-target"> </div>
  138.  
  139.  
  140. <hr class="wp-block-separator has-text-color has-background has-black-background-color has-black-color is-style-wide" />
  141.  
  142.  
  143. <h2 class="wp-block-heading"><strong>References</strong></h2>
  144.  
  145.  
  146.  
  147. [1] Nordquist H, Jamil RT. Biochemistry, HLA Antigens. Updated 24 Apr 2023. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; Jan 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK546662/</p>
  148.  
  149.  
  150.  
  151. [2] Bray, RA, et al. National Marrow Donor Program HLA Matching Guidelines for Unrelated Adult Donor Hematopoietic Cell Transplants. Transplantation and Cellular Therapy. 2008 Sep. Available from: https://www.astctjournal.org/article/S1083-8791(08)00274-7/fulltext</p>
  152.  
  153.  
  154.  
  155. [3] “Graft-Versus-Host Disease.” Leukemia &#038; Lymphoma Society. Accessed on 31 Dec 2023. Available from: https://www.lls.org/treatment/types-treatment/stem-cell-transplantation/graft-versus-host-disease</p>
  156.  
  157.  
  158.  
  159. [4] Bray, RA and Hurley, C. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 14. 45-53. 10.1016/j.bbmt.2008.06.014. https://www.researchgate.net/publication/23188666_National_Marrow_Donor_Program_HLA_Matching_Guidelines_for_Unrelated_Adult_Donor_Hematopoietic_Cell_Transplants</p>
  160.  
  161.  
  162.  
  163. [5] Jin, P., Wang, E. Polymorphism in clinical immunology – From HLA typing to immunogenetic profiling. J Transl Med 1, 8 (2003). https://doi.org/10.1186/1479-5876-1-8
  164. https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-1-8</p>
  165. ]]></content:encoded>
  169. </item>
  170. <item>
  171. <title>Study Reveals T Cells Capable of Targeting Multiple Tumor Antigens Simultaneously</title>
  172. <link>https://cytologicsbio.com/study-reveals-tcells-capable-of-targeting-multiple-tumor-antigens-simultaneously/</link>
  174. <dc:creator><![CDATA[Cytologics]]></dc:creator>
  175. <pubDate>Sun, 27 Aug 2023 05:52:18 +0000</pubDate>
  176. <category><![CDATA[News]]></category>
  177. <category><![CDATA[Scientific Knowledge]]></category>
  178. <category><![CDATA[Cell Therapy]]></category>
  179. <category><![CDATA[Immunology]]></category>
  180. <category><![CDATA[T cells]]></category>
  181. <category><![CDATA[TIL Therapy]]></category>
  182. <guid isPermaLink="false">https://cytologicsbio.com/?p=57074</guid>
  183.  
  184. <description><![CDATA[The adaptive immune system comprises specialized cells and biochemical pathways that are designed to target and destroy pathogens and tumor [&#8230;]]]></description>
  185. <content:encoded><![CDATA[
  186. <p style="font-size: 18px;">The adaptive immune system comprises specialized cells and biochemical pathways that are designed to target and destroy pathogens and tumor cells. This is generally achieved by recognizing cells that express abnormal protein markers resulting from changes induced by invading organisms or tumor transformation.</p>
  187. <p style="font-size: 18px;">The primary cell type involved in the destruction of infected or tumor cells are <a href="https://www.nature.com/articles/nri819" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">cytotoxic T cells.</span></mark></a><sup><a href="#references">[1]</a></sup> Immunotherapies involving the expansion and engineering of specialized cytotoxic T cells has been employed for nearly a decade.</p>
  188. <p style="font-size: 18px;">In the case of tumor-cell targeting, the prevailing view among immunologists has been that individual T cells can <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116355/" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">only recognize one specific tumor antigen.</span></mark></a><sup><a href="#references">[2]</a></sup>  However, a new study on tumor infiltrating lymphocytes (TILs) suggests certain T cells may actually be capable of targeting multiple tumor antigens.</p>
  189.  
  190.  
  191.  
  192.  
  193.  
  194. <h2 class="wp-block-heading">Study Background</h2>
  195.  
  196.  
  197.  
  198. <p style="font-size: 18px;">Research conducted by a collaborative group from Herlev Hospital in Denmark and Cardiff University in the UK has uncovered the astonishing existence of <a href="https://www.cell.com/cell/pdf/S0092-8674(23)00696-7.pdf" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">single T cells capable of recognizing different tumor antigens.</span></mark></a><sup><a href="#references">[3]</a></sup></p>
  199.  
  200.  
  201.  
  202. <p style="font-size: 18px;">The researchers wanted to understand the biological differences between patients with successful immunotherapy outcomes and those who did not clear cancers. The study involved a few patients who had stage IV melanoma and treated via tumor infiltrating lymphocyte therapy (TIL therapy).</p>
  203.  
  204.  
  205.  
  206. <p style="font-size: 18px;">TILs are tumor-penetrating T cells that recognize tumor cells as abnormal. For TIL therapy, TILs are collected from a surgically resected or biopsied tumor and expanded in the laboratory. The large number of TILs are then infused back into the patient.</p>
  207.  
  208.  
  209.  
  210. <figure class="wp-block-image size-medium"><img fetchpriority="high" decoding="async" class="wp-image-52091" src="https://cytologicsbio.com/wp-content/uploads/2023/08/Tumer-Infiltrating-Lymphocyte-T-cells.jpg" alt="Multiprong T Cells" width="500" height="500" />
  211. <figcaption>Credit: Cell (2023). DOI: 10.1016/j.cell.2023.06.020.</figcaption>
  212. </figure>
  213.  
  214.  
  215.  
  216. <div class="wp-block-spacer" style="height: 15px;" aria-hidden="true"> </div>
  217.  
  218.  
  219.  
  220. <h2 class="wp-block-heading">Discovery of “Multiprong” T Cells</h2>
  221.  
  222.  
  223.  
  224. <p style="font-size: 18px;">The study entailed analyzing the TIL infusion source of patients who achieved long-term remission of melanoma to determine the antigens targeted by the T cells. <a href="https://academic.oup.com/chromsci/article/55/2/182/2333796" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">Proteomic technologies</span></mark></a> were used to identify cancer-related epitopes recognized by the T cells.<sup><a href="#references">[4]</a></sup></p>
  225.  
  226.  
  227.  
  228. <p style="font-size: 18px;">T cell clones within the TIL infusion product were found to respond to three different antigen epitopes simultaneously. Two of the discovered recognized epitopes are newly identified. The cancer-specific T cell receptors were found to persist years after the TIL therapy.</p>
  229.  
  230.  
  231.  
  232. <p style="font-size: 18px;">Also striking is that the tumor-associated antigen recognition was additive, resulting in superior tumor cell recognition compared to that of conventional T cells that only recognize one antigen. The observation that these “multiprong” T cells are not found in patients whose cancer progresses despite treatment suggests that these T cells are key to cancer clearance or remission.</p>
  233.  
  234.  
  235.  
  236. <div class="wp-block-spacer" style="height: 18px;" aria-hidden="true"> </div>
  237.  
  238.  
  239.  
  240. <div class="wp-block-buttons has-custom-font-size is-content-justification-center is-layout-flex wp-container-core-buttons-is-layout-3 wp-block-buttons-is-layout-flex" style="font-size: 18px;">
  241. <div class="wp-block-button"><a class="wp-block-button__link has-luminous-vivid-orange-background-color has-background wp-element-button" href="https://cytologicsbio.com/recent-breakthroughs-in-off-the-shelf-nk-cells-for-cancer-immunotherapy/"><strong>RELATED CONTENT: Off-the-Shelf NK Cells for Cancer Immunotherapy</strong></a></div>
  242. </div>
  243.  
  244.  
  245.  
  246. <div class="wp-block-spacer" style="height: 32px;" aria-hidden="true"> </div>
  247.  
  248.  
  249.  
  250. <h2 class="wp-block-heading">Implications for Future Immunotherapies</h2>
  251.  
  252.  
  253.  
  254. <p style="font-size: 18px;">Cancer cells can <a href="https://cytologicsbio.com/understanding-the-importance-of-hla-in-emerging-immunotherapies/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">stop expressing an antigen recognized by conventional T cells,</span></mark></a>and this evading mechanism allows the cancer to continue to expand in a patient.<sup><a href="#references">[5]</a></sup></p>
  255.  
  256.  
  257.  
  258. <p style="font-size: 18px;">This biological advantage of cancer cells could be overcome by T cells that can recognize multiple cancer cell antigens. The discovery of individual T cells that can simultaneously recognize more than one tumor antigen can lead to the development of superior cancer-fighting tools for the oncologist.</p>
  259. <p style="font-size: 18px;">The discovered multiprong T cells can recognize multiple epitopes on the surface of a cancer cell; therefore, immunotherapies based on multiprong T cells can increase the efficacy of cancer-clearing therapies. These cells could also enhance the ability to design treatments that can target different types of cancers.</p>
  260. <p style="font-size: 18px;">Given the small number of patients in the reported study, one with a larger number of TIL-treated survivor participants would be valuable in better defining the multiprong T cell population and validate the findings.</p>
  261.  
  262.  
  263.  
  264. <p style="font-size: 18px;">If you’re interested in learning more on this topic, then check out some of our related content on <a href="https://cytologicsbio.com/tag/cell-therapy/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">emerging cell therapies</span></mark></a> and <a href="https://cytologicsbio.com/tag/t-cells/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">biology of T cells.</span></mark></a></p>
  265.  
  266.  
  267.  
  268. <div id="references" class="wp-block-ps2id-block-target"> </div>
  269.  
  270.  
  271. <hr class="wp-block-separator has-alpha-channel-opacity is-style-wide" />
  272.  
  273.  
  274. <h2 class="wp-block-heading">References</h2>
  275.  
  276.  
  277.  
  278. [1] Barry, M., Bleackley, R. Cytotoxic T lymphocytes: all roads lead to death. Nat Rev Immunol 2, 401–409 (2002). https://doi.org/10.1038/nri819.</p>
  279.  
  280.  
  281.  
  282. <p>&nbsp;</p>
  283.  
  284.  
  285.  
  286. [2] Zamora AE, Crawford JC, Thomas PG. Hitting the Target: How T Cells Detect and Eliminate Tumors. J Immunol. 2018 Jan 15;200(2):392-399. doi: 10.4049/jimmunol.1701413. PMID: 29311380; PMCID: PMC6116355.</p>
  287.  
  288.  
  289.  
  290. <p>&nbsp;</p>
  291.  
  292.  
  293.  
  294. [3] Dolton et al., 2023, Cell 186, 3333–3349 August 3, 2023 ª 2023 The Authors. Published by Elsevier Inc. https://doi.org/10.1016/j.cell.2023.06.020.</p>
  295.  
  296.  
  297.  
  298. <p>&nbsp;</p>
  299.  
  300.  
  301.  
  302. [4] Bilal Aslam and others, Proteomics: Technologies and Their Applications, Journal of Chromatographic Science, Volume 55, Issue 2, 1 February 2017, Pages 182–196, https://doi.org/10.1093/chromsci/bmw167.</p>
  303.  
  304.  
  305.  
  306. <p>&nbsp;</p>
  307.  
  308.  
  309.  
  310. [5] Kim SK, Cho SW. The Evasion Mechanisms of Cancer Immunity and Drug Intervention in the Tumor Microenvironment. Front Pharmacol. 2022 May 24;13:868695. doi: 10.3389/fphar.2022.868695.</p>
  311. ]]></content:encoded>
  315. </item>
  316. <item>
  317. <title>[E-BOOK] Peripheral Blood Mononuclear Cells: Guide on Cell Biology and Function</title>
  318. <link>https://cytologicsbio.com/e-book-peripheral-blood-mononuclear-cells-guide-on-cell-biology-and-function/</link>
  320. <dc:creator><![CDATA[Cytologics]]></dc:creator>
  321. <pubDate>Sun, 11 Jun 2023 15:58:17 +0000</pubDate>
  322. <category><![CDATA[Scientific Knowledge]]></category>
  323. <category><![CDATA[Technical Resources]]></category>
  324. <category><![CDATA[eBook]]></category>
  325. <category><![CDATA[PBMC]]></category>
  326. <guid isPermaLink="false">https://cytologicsbio.com/?p=57020</guid>
  327.  
  328. <description><![CDATA[eBook Overview Peripheral blood mononuclear cells (PBMCs) include lymphocytes, monocytes and dendritic cells and can be used in a variety [&#8230;]]]></description>
  329. <content:encoded><![CDATA[
  330. <h2 class="wp-block-heading has-text-align-left">eBook Overview</h2>
  331.  
  332.  
  333.  
  334. <p style="font-size: 18px; line-height: 1.5;">Peripheral blood mononuclear cells (PBMCs) include lymphocytes, monocytes and dendritic cells and can be used in a variety of cell-based assays. <a href="https://cytologicsbio.com/buy-human-peripheral-blood-mononuclear-cells-pbmcs/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">PBMCs</span></mark></a> are critical for immunology research and clinical applications such as cell therapy and vaccine development due to their ability to provide valuable insights into immune responses in humans.</p>
  335. <p style="font-size: 18px; line-height: 1.5;">The objective of this eBook is to provide a quick reference resource to scientists who need to isolate and culture PBMCs or develop assays to study their function. Research scientists transitioning from animal to human studies could find this to be a particularly useful reference.</p>
  336.  
  337.  
  338.  
  339. <div class="wp-block-columns is-layout-flex wp-container-core-columns-is-layout-2 wp-block-columns-is-layout-flex">
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  344. <div class="wp-block-button has-custom-width wp-block-button__width-75 has-custom-font-size" style="font-size: 18px;"><a class="wp-block-button__link has-luminous-vivid-orange-background-color has-background has-text-align-center wp-element-button" href="https://cytologicsbio.com/peripheral-blood-mononuclear-cells-ebook/"><strong>Download PBMC eBook</strong></a></div>
  345. </div>
  346. </div>
  347.  
  348.  
  349.  
  350. <div class="wp-block-column is-vertically-aligned-center is-layout-flow wp-block-column-is-layout-flow" style="flex-basis: 33.33%;"><div class="wp-block-image">
  351. <figure class="aligncenter size-medium is-resized"><a href="https://cytologicsbio.com/peripheral-blood-mononuclear-cells-ebook/"><img decoding="async" class="wp-image-57008" src="https://cytologicsbio.com/wp-content/uploads/2023/06/PBMC-ebook-cover-open-300x196.jpg" alt="PBMC ebook open pages" width="225" height="147" srcset="https://cytologicsbio.com/wp-content/uploads/2023/06/PBMC-ebook-cover-open-300x196.jpg 300w, https://cytologicsbio.com/wp-content/uploads/2023/06/PBMC-ebook-cover-open-600x392.jpg 600w, https://cytologicsbio.com/wp-content/uploads/2023/06/PBMC-ebook-cover-open.jpg 613w" sizes="(max-width: 225px) 100vw, 225px" /></a></figure></div></div>
  352. </div>
  353. </div>
  354. </div>
  355.  
  356.  
  357.  
  358. <p style="font-size: 18px; line-height: 1.5;">Given how valuable PBMCs are to research, it’s important for scientists to have a thorough understanding of the development, function and activation processes of each cell type. This eBook contains summaries on the following:</p>
  359.  
  360.  
  361.  
  362. <ul style="font-size: 18px; line-height: 1.5;">
  363. <li>Basic biology and function of each PBMC subset</li>
  364. <li>Lymphocyte activation processes</li>
  365. <li>Frequency of each cell type in peripheral blood</li>
  366. <li>Recent advances in immunotherapies involving PBMCs</li>
  367. </ul>
  368. <p>&nbsp;</p>
  369. <p style="font-size: 18px; line-height: 1.5;"><strong><span class="has-inline-color has-vivid-cyan-blue-color"><span style="text-decoration: underline;"><a href="https://cytologicsbio.com/peripheral-blood-mononuclear-cells-ebook/" target="_blank" rel="noreferrer noopener">Click here to download our FREE eBook on PBMCs</a></span></span></strong></p>
  370.  
  371.  
  372.  
  373. <h4 class="wp-block-heading has-text-align-center has-white-color has-text-color has-background" style="background-color: #004aad;"><strong>Interested in an Easier Way to Source PBMCs?</strong></h4>
  374.  
  375.  
  376.  
  377. <p style="font-size: 18px; line-height: 1.5;">PBMC isolation is a critical step in the preparation of human immune cells for use in downstream research assays and applications. Donor recruitment, sample collection, and cell isolation and cryopreservation are tedious and time-consuming processes. Many researchers work with human specimen suppliers like Cytologics as a fast and cost-effective way to source PBMCs. Our validated methods and quality control procedures ensure you’ll receive high quality cells resulting in minimal variability in your experimental protocols.</p>
  378.  
  379.  
  380.  
  381. <div class="wp-block-buttons is-content-justification-center is-layout-flex wp-container-core-buttons-is-layout-5 wp-block-buttons-is-layout-flex">
  382. <div class="wp-block-button has-custom-width wp-block-button__width-50 has-custom-font-size" style="font-size: 18px;"><a class="wp-block-button__link has-luminous-vivid-orange-background-color has-background wp-element-button" href="https://cytologicsbio.com/product-category/pbmc/"><strong>Shop PBMCs Now</strong></a></div>
  383. </div>
  384.  
  385.  
  386. <hr class="wp-block-separator has-text-color has-black-color has-alpha-channel-opacity has-black-background-color has-background is-style-default" />
  387.  
  388.  
  389. <div class="wp-block-spacer" style="height: 18px;" aria-hidden="true"> </div>
  390.  
  391.  
  392.  
  393. <h2 class="wp-block-heading">References</h2>
  394.  
  395.  
  396.  
  397. [1] Betsou, F., Gaignaux, A., Ammerlaan, W. <em>et al.</em> <a href="https://link.springer.com/article/10.1007/s40139-019-00192-8" target="_blank" rel="noopener">Biospecimen Science of Blood for Peripheral Blood Mononuclear Cell (PBMC) Functional Applications</a>. <em>Curr Pathobiol Rep</em> <strong>7, </strong>17–27 (2019). https://doi.org/10.1007/s40139-019-00192-8</p>
  398. ]]></content:encoded>
  402. </item>
  403. <item>
  404. <title>3 Advantages of Using Pooled PBMCs to Detect and Quantify Pyrogens</title>
  405. <link>https://cytologicsbio.com/3-advantages-of-using-pooled-pbmcs-to-detect-and-quantify-pyrogens/</link>
  407. <dc:creator><![CDATA[Cytologics]]></dc:creator>
  408. <pubDate>Sun, 12 Mar 2023 23:21:37 +0000</pubDate>
  409. <category><![CDATA[Technical Resources]]></category>
  410. <category><![CDATA[Pooled PBMCs]]></category>
  411. <category><![CDATA[Regulations]]></category>
  412. <guid isPermaLink="false">https://cytologicsbio.com/?p=56887</guid>
  413.  
  414. <description><![CDATA[The primary method of testing pharmaceuticals for pyrogens since the 1960s has been the limulus amoebocyte lysate (LAL) test, which [&#8230;]]]></description>
  415. <content:encoded><![CDATA[
  416. <p style="font-size: 18px;">The primary method of testing pharmaceuticals for pyrogens since the 1960s has been the <a href="https://www.frontiersin.org/articles/10.3389/fmars.2020.582132/full" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">limulus amoebocyte lysate (LAL) test,</span></mark></a> which contains a reagent derived from the blood of Atlantic horseshoe crabs.<sup>[<a href="#references">1</a>]</sup> LAL has the unusual property of clotting at the presence of bacterial endotoxins and was therefore a useful in testing pharmaceuticals and medical devices that contact blood or cerebrospinal fluid.</p>
  417.  
  418.  
  419.  
  420. <p style="font-size: 18px;">Extensive harvesting of horseshoe crabs for this type of testing and biomedical research led to a decline in natural populations, causing many states and organizations to introduce quotas and other preservation regulations.</p>
  421.  
  422.  
  423.  
  424. <p style="font-size: 18px;">By testing with <a href="https://cytologicsbio.com/product/pooled-pbmcs/" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">pooled human peripheral blood mononuclear cells (PBMCs)</span></mark></a> instead of LAL, you can play in important role in the conservation of the horseshoe crab and utilize a methodology that is more effective at detecting and quantifying pyrogens.</p>
  425.  
  426.  
  427.  
  428. <h2 class="wp-block-heading">Advantage #1: Compliance with Future Regulations</h2>
  429.  
  430.  
  431.  
  432. <p style="font-size: 18px;">Using pooled PBMCs allows you to be proactive in switching from horseshoe crab-dependent LAL testing to more sustainable alternatives, positioning your company for compliance with future anti-animal testing regulations.</p>
  433.  
  434.  
  435.  
  436. <p style="font-size: 18px;">The current worldwide horseshoe crab population <a href="https://www.frontiersin.org/articles/10.3389/fmars.2018.00185/full" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">cannot sustainably support the growing demand</span></mark></a> for their blood by the life sciences, pharmaceutical, and medical device industries.<sup>[<a href="#references">2</a>]</sup> As a result, there is increasing interest in legally protecting horseshoe crabs and other animals from testing, particularly in Europe. <a href="http://www.asmfc.org/" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">The Atlantic States Marine Fisheries Commission (ASMFC)</span></mark></a> already takes biomedical collection into account in their overall collection quotas.</p>
  437.  
  438.  
  439.  
  440. <h2 class="wp-block-heading">Advantage #2: Better Detection and Quantification of Pyrogens</h2>
  441.  
  442.  
  443.  
  444. <p style="font-size: 18px;">With mounting pressure to reduce the use of animals for drug testing, the Monocyte Activation Test (MAT) has emerged as a logical alternative to LAL. In fact, MAT detects pyrogens that are not detected by LAL, making it a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136467/" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">more efficient and comprehensive test.</span></mark></a><sup>[<a href="#references">3</a>]</sup></p>
  445.  
  446.  
  447.  
  448. <p style="font-size: 18px;">MAT requires the use of PBMCs pooled from multiple human donors, which can <a href="https://pdfs.semanticscholar.org/36fa/1f15f8dad0fb459d187953047da025e9467e.pdf" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">detect pyrogens other than bacterial endotoxins,</span></mark></a> such as viral DNA and RNA bacterial glycan, lipopeptides, and other substances.<sup>[<a href="#references">4</a>]</sup> By testing with pooled PBMCs, you are utilizing the most relevant and broad detection system available.</p>
  449.  
  450.  
  451.  
  452. <p style="font-size: 18px;">Moving forward, MAT will likely replace LAL as the standard for pyrogen testing.</p>
  453.  
  454.  
  455.  
  456. <figure class="wp-block-image size-large"><img decoding="async" width="1024" height="525" class="wp-image-56910" src="https://cytologicsbio.com/wp-content/uploads/2023/03/Monocyte-Activation-Test-Cells-1024x525.jpg" alt="Pooled PBMCs detecting pyrogens" srcset="https://cytologicsbio.com/wp-content/uploads/2023/03/Monocyte-Activation-Test-Cells-1024x525.jpg 1024w, https://cytologicsbio.com/wp-content/uploads/2023/03/Monocyte-Activation-Test-Cells-600x308.jpg 600w, https://cytologicsbio.com/wp-content/uploads/2023/03/Monocyte-Activation-Test-Cells-300x154.jpg 300w, https://cytologicsbio.com/wp-content/uploads/2023/03/Monocyte-Activation-Test-Cells-768x394.jpg 768w, https://cytologicsbio.com/wp-content/uploads/2023/03/Monocyte-Activation-Test-Cells-1536x788.jpg 1536w, https://cytologicsbio.com/wp-content/uploads/2023/03/Monocyte-Activation-Test-Cells.jpg 2006w" sizes="(max-width: 1024px) 100vw, 1024px" /></figure>
  457.  
  458.  
  459.  
  460. <div class="wp-block-spacer" style="height: 18px;" aria-hidden="true"> </div>
  461.  
  462.  
  463.  
  464. <h2 class="wp-block-heading">Advantage #3: Reduce Donor-to-Donor Variability</h2>
  465.  
  466.  
  467.  
  468. <p style="font-size: 18px;">The <a href="https://www.edqm.eu/en/european-pharmacopoeia" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">European Pharmacopoeia’s guidelines</span></mark></a> for the MAT recommend pooling PBMC from at least four donors to reduce the effects of donor-to-donor variability. Although a pool of four donors is the minimum recommendation, up to eight donors may be used to obtain optimal results.</p>
  469.  
  470.  
  471.  
  472. <p style="font-size: 18px;">While most donors respond to bacterial endotoxins, there is greater variation in responses to other pyrogens. Including more donors in your PBMC sample increases the chance that all contaminants will be detected.</p>
  473.  
  474.  
  475.  
  476. <p style="font-size: 18px;">Our blood donors avoid anti-inflammatory medications before donation and are tested for blood borne pathogens such as HIV, Hepatitis B, and Hepatitis C to prevent lab-acquired infections. Pooled PBMCs from Cytologics have been widely used in the pharmaceutical industry for MAT with exceptional results.</p>
  477.  
  478.  
  479.  
  480. <h2 class="wp-block-heading">Want to Learn More?</h2>
  481.  
  482.  
  483.  
  484. <p style="font-size: 18px;">Have more questions about pooled PBMCs and how to use them? Then contact us by clicking the link below and a member of our team will respond immediately!</p>
  485.  
  486.  
  487.  
  488. <div class="wp-block-spacer" style="height: 12px;" aria-hidden="true"> </div>
  489.  
  490.  
  491.  
  492. <div class="wp-block-buttons is-layout-flex wp-block-buttons-is-layout-flex">
  493. <div class="wp-block-button has-custom-font-size aligncenter" style="font-size: 18px;"><a class="wp-block-button__link has-luminous-vivid-orange-background-color has-background wp-element-button" href="https://cytologicsbio.com/contact/"><strong>Contact Us</strong></a></div>
  494. </div>
  495.  
  496.  
  497.  
  498. <div class="wp-block-spacer" style="height: 12px;" aria-hidden="true"> </div>
  499.  
  500.  
  501.  
  502. <div id="references" class="wp-block-ps2id-block-target"> </div>
  503.  
  504.  
  505. <hr class="wp-block-separator has-alpha-channel-opacity is-style-default" />
  506.  
  507.  
  508. <h2 class="wp-block-heading">References</h2>
  509.  
  510.  
  511.  
  512. [1] Gorman R (2020) Atlantic Horseshoe Crabs and Endotoxin Testing: Perspectives on Alternatives, Sustainable Methods, and the 3Rs (Replacement, Reduction, and Refinement). <em>Front. Mar. Sci. </em>7:582132. doi: 10.3389/fmars.2020.582132</p>
  513.  
  514.  
  515.  
  516. [2] Krisfalusi-Gannon J, Ali W, Dellinger K, Robertson L, Brady TE, Goddard MKM, Tinker-Kulberg R, Kepley CL and Dellinger AL (2018) The Role of Horseshoe Crabs in the Biomedical Industry and Recent Trends Impacting Species Sustainability. <em>Front. Mar. Sci.</em> 5:185. doi: 10.3389/fmars.2018.00185</p>
  517.  
  518.  
  519.  
  520. [3] Solati S, Zhang T, Timman S. The monocyte activation test detects potentiated cytokine release resulting from the synergistic effect of endotoxin and non-endotoxin pyrogens. Innate Immun. 2022 Apr;28(3-4):130-137. doi: 10.1177/17534259221097948. Epub 2022 May 2. PMID: 35491666; PMCID: PMC9136467.</p>
  521.  
  522.  
  523.  
  524. [4] Hasiwa N, et al. Evidence for the Detection of Non-Endotoxin Pyrogens by the Whole Blood Monocyte Activation Test. Alternatives to Animal Experimentation (ALTEX). Feb. 2013.</p>
  525. ]]></content:encoded>
  529. </item>
  530. <item>
  531. <title>Monocytes: A Critical Link between Periodontal Disease and Cardiovascular Disease</title>
  532. <link>https://cytologicsbio.com/monocytes-a-critical-link-between-periodontal-disease-and-cardiovascular-disease/</link>
  534. <dc:creator><![CDATA[Cytologics]]></dc:creator>
  535. <pubDate>Sun, 22 Jan 2023 16:46:55 +0000</pubDate>
  536. <category><![CDATA[News]]></category>
  537. <category><![CDATA[Scientific Knowledge]]></category>
  538. <category><![CDATA[Cardiovascular Disease]]></category>
  539. <category><![CDATA[Monocytes]]></category>
  540. <guid isPermaLink="false">https://cytologicsbio.com/?p=56811</guid>
  541.  
  542. <description><![CDATA[Cardiovascular disease is the leading cause of death worldwide, and a number of risk factors have been identified including, but [&#8230;]]]></description>
  543. <content:encoded><![CDATA[
  544. <p style="font-size: 18px;">Cardiovascular disease is the leading cause of death worldwide, and a number of risk factors have been identified including, but not limited to, diet, obesity, smoking, and physical activity. Certain biological processes, such as inflammation, have also been found to impact the development of atherosclerosis.</p>
  545.  
  546.  
  547.  
  548. <p style="font-size: 18px;">Periodontitis, in particular, is an inflammatory condition linked to the development of atherosclerosis-related cardiovascular disease. <a href="https://www.nidcr.nih.gov/research/data-statistics/periodontal-disease/adults" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">Periodontal disease</span></mark></a> is a serious infection of the gums that affects up to 40% of the U.S. population.<sup><a href="#references">[1]</a></sup> The disease is caused by bacteria that accumulate on the teeth and gums, typically due to poor dental hygiene.</p>
  549.  
  550.  
  551.  
  552. <p style="font-size: 18px;">Although periodontal disease is a well-known risk <mark class="has-inline-color has-black-color" style="background-color: rgba(0, 0, 0, 0);">factor</mark> for cardiovascular disease, the exact mechanism connecting the two diseases has been debated for decades.<sup><a href="#references">[2]</a></sup> A number of pathomechanisms have been studied with plausible conclusions on why periodontal pathogens are commonly found in atherosclerotic plaques. However, a growing body of scientific evidence points to <a href="https://cytologicsbio.com/product/cd14-monocytes/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">monocytes</span></mark></a> as the key to understanding the direct and indirect relationships between periodontal disease and cardiovascular disease.</p>
  553.  
  554.  
  555.  
  556.  
  557.  
  558. <h2 class="wp-block-heading">Introduction and Background Research</h2>
  559.  
  560.  
  561.  
  562. <p style="font-size: 18px;">Scientists have considered a number of mechanisms for the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276050/" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">periodontitis-related development of atherosclerosis,</span></mark></a> such as involvement of cytokine release induced by dental plaque bacteria and innate immunity activated by bacteremia from dental procedures.<sup><a href="#references">[3]</a></sup></p>
  563.  
  564.  
  565.  
  566. <p style="font-size: 18px;">Periodontal disease and atherosclerosis formation may be linked directly via the entry of dental plaque microorganisms into damaged endothelial walls. However, an indirect mechanism may involve the activation of inflammatory molecules induced by the periodontitis condition.</p>
  567.  
  568.  
  569.  
  570. <p style="font-size: 18px;">Peripheral blood monocytes of the innate immune system are capable of triggering both periodontal and atherosclerotic diseases. Published data details the presence of <a href="https://pubmed.ncbi.nlm.nih.gov/23046009/" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">phenotypic changes in peripheral blood monocytes</span></mark></a> in patients with periodontitis, for example, a predominance of T-helper-2 cell responses compared to T-helper-1 responses.<sup><a href="#references">[4]</a></sup> Monocytes have been found in an activated state in atherosclerosis and show increased inflammatory response profiles.</p>
  571.  
  572.  
  573.  
  574. <h2 class="wp-block-heading">Role of Monocytes in Periodontal Disease and Cardiovascular Disease</h2>
  575.  
  576.  
  577.  
  578. <p style="font-size: 18px;">Multiple <em>in vivo</em> studies have revealed that induced periodontitis leads to the activation of peripheral blood monocytes and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578868/" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">upregulation of TNF-alpha and IL-6 proinflammatory genes.</span></mark></a><sup><a href="#references">[5]</a></sup> This upregulation enhances the adhesion of the monocytes to aortic endothelial walls and triggers atherosclerosis development.</p>
  579.  
  580.  
  581.  
  582. <p style="font-size: 18px;">Observations from these studies have established peripheral blood monocytes as an important link between periodontitis and atherosclerotic cardiovascular disease, but the molecular mechanisms underpinning this linkage were unknown until recently.</p>
  583.  
  584.  
  585.  
  586. <p style="font-size: 18px;">In 2021, a global team of researchers led by Dr. Wanchen Ning of Southern Medical University in Guangzhou conducted a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664523/" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">bioinformatics study</span></mark></a> analyzing public gene expression profile datasets of peripheral blood monocytes.<sup><a href="#references">[6]</a></sup></p>
  587.  
  588.  
  589.  
  590. <p style="font-size: 18px;">The researchers accessed public gene expression data of peripheral blood monocytes that were obtained from patients with periodontitis and from those with atherosclerosis. The analysis uncovered 165 differentially expressed genes that are dysregulated in both periodontitis and atherosclerosis, and a number of the genes may play a role in crosstalk between the two disease states.</p>
  591.  
  592.  
  593.  
  594. <p style="font-size: 18px;">Examples of biological processes associated with the identified genes include activation of neutrophils, regulation of leukocyte activation, and vascular endothelial growth factor signaling.</p>
  595.  
  596.  
  597.  
  598. <p style="font-size: 18px;">Results of additional expression profile analysis indicate cellular responses to reactive oxygen species and elevated oxygen levels for both disease processes, suggesting that oxidative stress is a shared phenomenon between periodontitis and atherosclerosis.</p>
  599.  
  600.  
  601.  
  602. <div class="wp-block-buttons has-custom-font-size is-content-justification-center is-layout-flex wp-container-core-buttons-is-layout-7 wp-block-buttons-is-layout-flex" style="font-size: 18px;">
  603. <div class="wp-block-button"><a class="wp-block-button__link has-luminous-vivid-orange-background-color has-background wp-element-button" href="https://cytologicsbio.com/role-of-regulatory-t-cells-in-coronary-artery-disease/"><strong>RELATED CONTENT: Role of Regulatory T Cells in Coronary Artery Disease</strong></a></div>
  604. </div>
  605.  
  606.  
  607.  
  608. <div class="wp-block-spacer" style="height: 17px;" aria-hidden="true"> </div>
  609.  
  610.  
  611.  
  612. <h2 class="wp-block-heading">Conclusion</h2>
  613.  
  614.  
  615.  
  616. <p style="font-size: 18px;">Overall, the monocyte gene expression analysis results suggest that bacterial invasion of epithelial cells, platelet activation, and the vascular endothelial growth factor signaling pathway represent the most significant processes linking periodontitis and atherosclerosis.</p>
  617.  
  618.  
  619.  
  620. <p style="font-size: 18px;">This information may form the basis for further research to determine biomarkers for risk assessment and implementation of preventive measures to lower risk of cardiovascular disease development in patients prone to periodontal disease states.</p>
  621.  
  622.  
  623.  
  624. <p style="font-size: 18px;">The data may also be valuable for researchers to identify targets for developing novel therapies for periodontal and cardiovascular diseases.</p>
  625.  
  626.  
  627.  
  628. <p style="font-size: 18px;">If you’re interested in learning more on this topic, then check out some of our related content on <a href="https://cytologicsbio.com/tag/monocytes/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">scientific research involving monocytes</span></mark></a> and <a href="https://cytologicsbio.com/tag/cardiovascular-disease/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">cardiovascular disease.</span></mark></a></p>
  629.  
  630.  
  631.  
  632. <div class="wp-block-spacer" style="height: 20px;" aria-hidden="true"> </div>
  633.  
  634.  
  635.  
  636. <div id="references" class="wp-block-ps2id-block-target"> </div>
  637.  
  638.  
  639. <hr class="wp-block-separator has-alpha-channel-opacity is-style-wide" />
  640.  
  641.  
  642. <h2 class="wp-block-heading">References</h2>
  643.  
  644.  
  645.  
  646. [1] Eke PI, Thornton-Evans GO, Wei L, Borgnakke WS, Dye BA, Genco RJ. Periodontitis in US Adults: National Health and Nutrition Examination Survey 2009-2014. J Am Dent Assoc. 2018 Jul;149(7):576-588.e6. doi: 10.1016/j.adaj.2018.04.023. PMID: 29957185; PMCID: PMC8094373.</p>
  647.  
  648.  
  649.  
  650. <p>&nbsp;</p>
  651.  
  652.  
  653.  
  654. [2] Faraedon Z, Sarhang G, Ali A, Aram S, Julian Y. Association Between Periodontal Disease and Atherosclerotic Cardiovascular Diseases: Revisited. Frontiers in Cardiovascular Medicine, Vol. 7. 2021 Jan 15; doi: 10.3389/fcvm.2020.625579.</p>
  655.  
  656.  
  657.  
  658. <p>&nbsp;</p>
  659.  
  660.  
  661.  
  662. [3] Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol. 2015 Jan;15(1):30-44. doi: 10.1038/nri3785. PMID: 25534621; PMCID: PMC4276050.</p>
  663.  
  664.  
  665.  
  666. <p>&nbsp;</p>
  667.  
  668.  
  669.  
  670. [4] Fokkema SJ. Peripheral blood monocyte responses in periodontitis. Int J Dent Hyg. 2012 Aug;10(3):229-35. doi: 10.1111/j.1601-5037.2012.00572.x. PMID: 23046009.</p>
  671.  
  672.  
  673.  
  674. <p>&nbsp;</p>
  675.  
  676.  
  677.  
  678. [5] Martínez-García M, Hernández-Lemus E. Periodontal Inflammation and Systemic Diseases: An Overview. Front Physiol. 2021 Oct 27;12:709438. doi: 10.3389/fphys.2021.709438. PMID: 34776994; PMCID: PMC8578868.</p>
  679.  
  680.  
  681.  
  682. <p>&nbsp;</p>
  683.  
  684.  
  685.  
  686. [6] Ning W, Ma Y, Li S, Wang X, Pan H, Wei C, Zhang S, Bai D, Liu X, Deng Y, Acharya A, Pelekos G, Savkovic V, Li H, Gaus S, Haak R, Schmalz G, Ziebolz D, Ma Y, Xu Y. Shared Molecular Mechanisms between Atherosclerosis and Periodontitis by Analyzing the Transcriptomic Alterations of Peripheral Blood Monocytes. Comput Math Methods Med. 2021 Dec 3;2021:1498431.</p>
  687. ]]></content:encoded>
  691. </item>
  692. <item>
  693. <title>Unlocking the Therapeutic Potential of Gamma Delta T Cells</title>
  694. <link>https://cytologicsbio.com/unlocking-the-therapeutic-potential-of-gamma-delta-t-cells/</link>
  696. <dc:creator><![CDATA[Cytologics]]></dc:creator>
  697. <pubDate>Mon, 28 Nov 2022 04:50:55 +0000</pubDate>
  698. <category><![CDATA[News]]></category>
  699. <category><![CDATA[Cell Therapy]]></category>
  700. <category><![CDATA[T cells]]></category>
  701. <guid isPermaLink="false">https://cytologicsbio.com/?p=56782</guid>
  702.  
  703. <description><![CDATA[Gamma delta T cells are a subset of T cells that promote the inflammatory responses and are an essential component [&#8230;]]]></description>
  704. <content:encoded><![CDATA[
  705. <p style="font-size: 18px;">Gamma delta T cells are a subset of T cells that promote the inflammatory responses and are an essential component of the immune system. Although gamma delta (γδ) T cells only comprise approximately <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140678/" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">5% of all T cells</span></mark></a> circulating in peripheral blood, they play an important role in fighting cancer.<sup>[<a href="#references">1</a>]</sup> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674957/" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">A recent study</span></mark></a> published in <em>OncoImmunology</em> revealed that the amount of gamma delta T cells that infiltrate a tumor was the best predictor of a favorable outcome for certain types of cancer patients.<sup>[<a href="#references">2</a>]</sup></p>
  706.  
  707.  
  708.  
  709. <p style="font-size: 18px;">Despite the critical role gamma delta T cells play in immunity, researchers do not fully understand the mechanisms that cause proinflammatory functions. Ongoing research involving gamma delta T cells indicates that these cells may hold the key to effective cell therapies that target solid tumors.</p>
  710.  
  711.  
  712.  
  713. <p style="font-size: 18px;">Unlike alpha beta T cells, gamma delta T cells do not require donor compatibility to <a href="https://www.nature.com/articles/s41423-020-0504-x" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">recognize the target cancer antigen.</span></mark></a><sup>[<a href="#references">3</a>]</sup> This feature makes gamma delta T cells ideal for off-the-shelf CAR-T therapies that are derived from donors instead of from the patient. An allogeneic approach involving gamma delta T cells could result in a more accessible, effective and affordable immunotherapy for patients.</p>
  714.  
  715.  
  716.  
  717.  
  718.  
  719. <h2 class="wp-block-heading">What Are Gamma Delta T Cells?</h2>
  720.  
  721.  
  722.  
  723. <p style="font-size: 18px;">The primary T cell type used for <a href="https://cytologicsbio.com/recent-developments-made-in-car-t-cell-therapies/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">CAR-T cell therapies</span></mark></a> are alpha beta T cells. These conventional T cells are dependent on major histocompatibility complex (MHC)-antigen presentation and display limited targeting of solid tumor cells.</p>
  724.  
  725.  
  726.  
  727. <p style="font-size: 18px;">Another T cell type, unconventional, or gamma delta T cells, express a unique T-cell receptor comprised of gamma and delta glycoprotein chains. Unlike alpha beta T cells, the gamma delta T cells are in much lower abundance in the body.</p>
  728.  
  729.  
  730.  
  731. <p style="font-size: 18px;">What also makes gamma delta T cells unique is that they can target tumor cells without the need for MHC-antigen presentation. Therefore, they can target cells through a <a href="https://www.frontiersin.org/articles/10.3389/fimmu.2022.894315/full" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">cytotoxic mechanism</span></mark></a> or by activating other immune cells.<sup>[<a href="#references">4</a>]</sup></p>
  732.  
  733.  
  734.  
  735. <h2 class="wp-block-heading">Advantages of Using Gamma Delta T Cells in Immunotherapies</h2>
  736.  
  737.  
  738.  
  739. <p style="font-size: 18px;">Immunotherapies based on T cells, especially CAR-T cells, have shifted the paradigm in how we treat cancer. These genetically-modified T cells have shown remarkable remission rates in patients with hematological cancers, particularly those who do not respond favorably to conventional treatments. However, the CAR-T cell approach is known for the risk of <a href="https://www.cancer.gov/about-cancer/treatment/research/car-t-cells" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">very serious side effects</span></mark></a>, limited ability to target solid tumors and scalability challenges.<sup>[<a href="#references">5</a>]</sup></p>
  740.  
  741.  
  742.  
  743. <p style="font-size: 18px;">Current and emerging CAR-T therapies are based on alpha beta T cells, which may be a source of the aforementioned limitations. Gamma delta T cells, on the other hand, are part of body&#8217;s <a href="https://cjasn.asnjournals.org/content/10/8/1459" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">innate immune response,</span></mark></a> which constitutes the first and faster line of defense of the immune system.<sup>[<a href="#references">6</a>]</sup></p>
  744.  
  745.  
  746. <div class="wp-block-image">
  747. <figure class="aligncenter size-large"><a href="https://cytologicsbio.com/neoantigen-t-cell-receptor-gene-therapy-for-pancreatic-cancer-shows-promise-in-clinical-trial/"><img decoding="async" width="1024" height="450" class="wp-image-56793" src="https://cytologicsbio.com/wp-content/uploads/2022/11/Neoantigen-T-cell-Receptor-Therapy-1024x450.jpg" alt="" srcset="https://cytologicsbio.com/wp-content/uploads/2022/11/Neoantigen-T-cell-Receptor-Therapy-1024x450.jpg 1024w, https://cytologicsbio.com/wp-content/uploads/2022/11/Neoantigen-T-cell-Receptor-Therapy-scaled-600x264.jpg 600w, https://cytologicsbio.com/wp-content/uploads/2022/11/Neoantigen-T-cell-Receptor-Therapy-300x132.jpg 300w, https://cytologicsbio.com/wp-content/uploads/2022/11/Neoantigen-T-cell-Receptor-Therapy-768x337.jpg 768w, https://cytologicsbio.com/wp-content/uploads/2022/11/Neoantigen-T-cell-Receptor-Therapy-1536x675.jpg 1536w, https://cytologicsbio.com/wp-content/uploads/2022/11/Neoantigen-T-cell-Receptor-Therapy-scaled.jpg 2048w" sizes="(max-width: 1024px) 100vw, 1024px" /></a></figure></div>
  748.  
  749.  
  750. <div class="wp-block-spacer" style="height: 24px;" aria-hidden="true"> </div>
  751.  
  752.  
  753.  
  754. <p style="font-size: 18px;">The lack of dependence on MHC-antigen presentation makes gamma delta T cells promising tools for the development of allogenic therapies that have a low risk of graft-versus-host disease.</p>
  755.  
  756.  
  757.  
  758. <p style="font-size: 18px;">Additionally, gamma delta T cells possess characteristics of both the innate and adaptive immune systems and express a number of receptors that are also found on <a href="https://cytologicsbio.com/natural-killer-cells-cell-biology-and-research-applications/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">natural killer cells</span></mark></a> that have enhanced recognition of tumor cells.</p>
  759.  
  760.  
  761.  
  762. <p style="font-size: 18px;">The unique characteristics of gamma delta T cells form the basis of current research in the development of immunotherapies, particularly those focusing on subtypes that infiltrate solid tumors (e.g., Vgamma1 and Vgamma2).</p>
  763.  
  764.  
  765.  
  766. <p style="font-size: 18px;">For example, results of research investigating gamma delta T-cell levels in <a href="https://europepmc.org/article/pmc/pmc9413168" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">patients with bladder cancer</span></mark></a> showed that high intratumor gamma delta T-cell proportions (possibly due to Vgamma2 T cells) were associated with better patient survival outcomes, suggesting that Vgamma2 T cells may have an important role in tumor control.<sup>[<a href="#references">7</a>]</sup></p>
  767.  
  768.  
  769.  
  770. <h2 class="wp-block-heading">Research on Therapeutic Applications</h2>
  771.  
  772.  
  773.  
  774. <p style="font-size: 18px;">Understanding the biology of gamma delta T cells may also unlock information that can be harnessed to develop treatments for cancer and cardiovascular disease, the leading causes of death worldwide.</p>
  775.  
  776.  
  777.  
  778. <h3 class="wp-block-heading">Cancer Treatment</h3>
  779.  
  780.  
  781.  
  782. <p style="font-size: 18px;">Given the inherent advantages of gamma delta T cells in targeting tumors, several therapeutic approaches (both allogeneic and autologous) have been developed to treat cancer. All of these therapies are currently in pre-clinical or clinical trial stages of development.</p>
  783.  
  784.  
  785.  
  786. <p style="font-size: 18px;">Since gamma delta T cells recognize tumor cells independently of HLA antigen presentation, allogeneic (or donor-derived) T-cells have proven to be <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245381/" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">relatively effective at triggering antitumor immunity</span></mark></a> with low risk of graft-versus-host disease (GvHD).<sup>[<a href="#references">8</a>]</sup></p>
  787.  
  788.  
  789.  
  790. <p style="font-size: 18px;">In addition to allogenic gamma delta T cell therapies, researchers have studied autologous approaches by incorporating the tumor-targeting mechanism of CAR-T technology with gamma delta T cells. Initial results from these targeted approaches (e.g., Vgamma1 and Vgamma2 studies described above) show great promise and confirm the safety of gamma delta T-cell-based strategies.</p>
  791.  
  792.  
  793.  
  794. <h3 class="wp-block-heading">Cardiovascular Disease</h3>
  795.  
  796.  
  797.  
  798. <p style="font-size: 18px;">Information gathered from studies examining the relationships of immune cell subsets with cardiac function suggests that immunomodulatory treatment approaches may help prevent heart failure in those at risk.</p>
  799.  
  800.  
  801.  
  802. <p style="font-size: 18px;"><a href="https://pubmed.ncbi.nlm.nih.gov/34236048/" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">A study measuring peripheral immune cell subsets</span></mark></a> was conducted in patients with atherosclerosis, and the association of the subsets with left ventricular global circumferential strain (a measure of left ventricular dysfunction) was determined.<sup>[<a href="#references">9</a>]</sup></p>
  803.  
  804.  
  805.  
  806. <p style="font-size: 18px;">The researchers found that the presence of higher proportions of gamma delta T cells was associated with a worse measure of left ventricular global circumferential strain. This insight may help in identifying targets for the developing immunomodulatory therapies to prevent heart failure in high-risk patient populations.</p>
  807.  
  808.  
  809.  
  810. <h2 class="wp-block-heading">Conclusion</h2>
  811.  
  812.  
  813.  
  814. <p style="font-size: 18px;">Gamma delta T-cell–based therapies can represent suitable, effective approaches to treat diverse disease states while minimizing serious adverse events. In the near future, results obtained from ongoing clinical trials will determine whether the potential of gamma delta T cells will be translated into clinical benefit.</p>
  815.  
  816.  
  817.  
  818. <p style="font-size: 18px;">To learn more on this topic, check out our recent articles on emerging <a href="https://cytologicsbio.com/tag/cell-therapy/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">cell &amp; gene therapies</span></mark></a> and <a href="https://cytologicsbio.com/tag/t-cells/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">T cells.</span></mark></a></p>
  819.  
  820.  
  821.  
  822. <p style="font-size: 18px;">We also offer custom cell processing services for researchers in the field of T-cell-based therapies &#8212; <a href="https://cytologicsbio.com/contact/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">contact us</span></mark></a> for more information or submit a custom request today!</p>
  823.  
  824.  
  825.  
  826. <div class="wp-block-spacer" style="height: 12px;" aria-hidden="true"> </div>
  827.  
  828.  
  829.  
  830. <div class="wp-block-buttons is-content-justification-center is-layout-flex wp-container-core-buttons-is-layout-8 wp-block-buttons-is-layout-flex">
  831. <div class="wp-block-button"><a class="wp-block-button__link has-luminous-vivid-orange-background-color has-background wp-element-button" href="https://cytologicsbio.com/custom-order/"><strong>Submit Custom Request</strong></a></div>
  832. </div>
  833.  
  834.  
  835.  
  836. <div class="wp-block-spacer" style="height: 12px;" aria-hidden="true"> </div>
  837.  
  838.  
  839.  
  840. <div id="references" class="wp-block-ps2id-block-target"> </div>
  841.  
  842.  
  843. <hr class="wp-block-separator has-alpha-channel-opacity is-style-wide" />
  844.  
  845.  
  846. <h2 class="wp-block-heading">References</h2>
  847.  
  848.  
  849.  
  850. [1] Parker C.M., Groh V., Band H., Porcelli S.A., Morita C., Fabbi M., Glass D., Strominger J.L., Brenner M.B. Evidence for extrathymic changes in the T cell receptor gamma/delta repertoire. J. Exp. Med. 1990;171:1597–1612. doi: 10.1084/jem.171.5.1597.</p>
  851.  
  852.  
  853.  
  854. <p>&nbsp;</p>
  855.  
  856.  
  857.  
  858. [2] Wang J, Lin C, Li H, Li R, Wu Y, Liu H, Zhang H, He H, Zhang W, Xu J. Tumor-infiltrating γδT cells predict prognosis and adjuvant chemotherapeutic benefit in patients with gastric cancer. Oncoimmunology. 2017 Jul 24;6(11):e1353858. doi: 10.1080/2162402X.2017.1353858. PMID: 29147601; PMCID: PMC5674957.</p>
  859.  
  860.  
  861.  
  862. <p>&nbsp;</p>
  863.  
  864.  
  865.  
  866. [3] Kabelitz, D., Serrano, R., Kouakanou, L. et al. Cancer immunotherapy with γδ T cells: many paths ahead of us. Cell Mol Immunol 17, 925–939 (2020). https://doi.org/10.1038/s41423-020-0504-x.</p>
  867.  
  868.  
  869.  
  870. <p>&nbsp;</p>
  871.  
  872.  
  873.  
  874. [4] Chan KF, Duarte JDG, Ostrouska S, Behren A. γδ T Cells in the Tumor Microenvironment-Interactions with Other Immune Cells. Front Immunol. 2022 Jul 11;13:894315.</p>
  875.  
  876.  
  877.  
  878. <p>&nbsp;</p>
  879.  
  880.  
  881.  
  882. [5] &#8220;CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers.&#8221; National Cancer Institute. Accessed via https://www.cancer.gov/about-cancer/treatment/research/car-t-cells.</p>
  883.  
  884.  
  885.  
  886. <p>&nbsp;</p>
  887.  
  888.  
  889.  
  890. [6] Hato T and Dagher PC. CJASN August 2015, 10 (8) 1459-1469; DOI: https://doi.org/10.2215/CJN.04680514.</p>
  891.  
  892.  
  893.  
  894. <p>&nbsp;</p>
  895.  
  896.  
  897.  
  898. [7] Nguyen S, Chevalier MF, Benmerzoug S, Cesson V, Schneider AK, Rodrigues-Dias SC, Dartiguenave F, Lucca I, Jichlinski P, Roth B, Nardelli-Haefliger D, Derré L. Vδ2 T cells are associated with favorable clinical outcomes in patients with bladder cancer and their tumor reactivity can be boosted by BCG and zoledronate treatments. J Immunother Cancer. 2022 Aug;10(8):e004880.</p>
  899.  
  900.  
  901.  
  902. <p>&nbsp;</p>
  903.  
  904.  
  905.  
  906. [8] Saura-Esteller J, de Jong M, King LA, Ensing E, Winograd B, de Gruijl TD, Parren PWHI, van der Vliet HJ. Gamma Delta T-Cell Based Cancer Immunotherapy: Past-Present-Future. Front Immunol. 2022 Jun 16;13:915837. doi: 10.3389/fimmu.2022.915837. PMID: 35784326; PMCID: PMC9245381.</p>
  907.  
  908.  
  909.  
  910. <p>&nbsp;</p>
  911.  
  912.  
  913.  
  914. [9] Sinha A, Rivera AS, Doyle MF, Sitlani C, Fohner A, Huber SA, Olson NC, Lima JA, Delaney JA, Feinstein MJ, Shah SJ, Tracy RP, Psaty BM. Association of immune cell subsets with cardiac mechanics in the Multi-Ethnic Study of Atherosclerosis. JCI Insight. 2021 Jul 8;6(13):e149193.</p>
  915. ]]></content:encoded>
  919. </item>
  920. <item>
  921. <title>CD14+ Monocytes: Cell Biology and Research Applications</title>
  922. <link>https://cytologicsbio.com/cd14-monocytes-cell-biology-and-research-applications/</link>
  924. <dc:creator><![CDATA[Cytologics]]></dc:creator>
  925. <pubDate>Mon, 17 Oct 2022 03:21:24 +0000</pubDate>
  926. <category><![CDATA[Scientific Knowledge]]></category>
  927. <category><![CDATA[Cell Biology]]></category>
  928. <category><![CDATA[Monocytes]]></category>
  929. <guid isPermaLink="false">https://cytologicsbio.com/?p=56646</guid>
  930.  
  931. <description><![CDATA[Monocytes are white blood cells that originate from the bone marrow. They are a crucial element of the innate immune [&#8230;]]]></description>
  932. <content:encoded><![CDATA[
  933. <p style="font-size: 18px;">Monocytes are white blood cells that originate from the bone marrow. They are a crucial element of the innate immune system. They can differentiate into monocyte-derived dendritic cells, tissue-resident macrophages, pro-inflammatory macrophages (M1), and anti-inflammatory macrophages (M2) based on cellular and cytokine signals. They <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726802/" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">regulate cell homeostasis,</span></mark></a> particularly in the setting of pathogens and inflammation.<sup>[<a href="#references">1</a>]</sup> In this article, we will describe the basic function and biology of monocytes, along with their applications in research and medicine.</p>
  934.  
  935.  
  936.  
  937.  
  938.  
  939. <h2 class="wp-block-heading">Introduction</h2>
  940.  
  941.  
  942.  
  943. <p style="font-size: 18px;">Human monocytes represent <a href="https://cytologicsbio.com/infographic-frequencies-of-cell-types-in-human-peripheral-blood/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">between 3%-10% of all the circulating nucleated cells in a healthy individual&#8217;s blood.</span></mark></a><sup>[<a href="#references">2</a>]</sup> Monocytes are classified into three main subsets: CD14+ CD16- monocytes known as classical, CD14(dim) CD16+ known as non-classical, and CD14+CD16+ known as intermediate. Each subtype is distinct from the other due to specific surface markers and functions in cellular homeostasis and disease.<sup>[<a href="#references">3</a>]</sup></p>
  944.  
  945.  
  946.  
  947. <p style="font-size: 18px;">CD14 is the primary marker of human monocytes. It is a glycoprotein and myelomonocytic differentiation antigen that acts as an <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850372/" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">auxiliary protein to toll-like receptor-4.</span></mark></a><sup>[<a href="#references">4</a>]</sup> During infections, pathogens bind to CD14 and TLR-4 receptors on the monocytes and trigger cytokine production, leading to inflammation and phagocytosis activation.<sup>[<a href="#references">5</a>]</sup></p>
  948.  
  949.  
  950.  
  951. <h3 class="wp-block-heading">Figure 1. Types of Monocytes by Immunological Function.</h3>
  952.  
  953.  
  954.  
  955. <figure class="wp-block-image size-large"><img decoding="async" width="1024" height="796" class="wp-image-56760" src="https://cytologicsbio.com/wp-content/uploads/2022/10/Types-of-Monocytes-1024x796.jpg" alt="Various types of monocytes and their immunological function" srcset="https://cytologicsbio.com/wp-content/uploads/2022/10/Types-of-Monocytes-1024x796.jpg 1024w, https://cytologicsbio.com/wp-content/uploads/2022/10/Types-of-Monocytes-600x467.jpg 600w, https://cytologicsbio.com/wp-content/uploads/2022/10/Types-of-Monocytes-300x233.jpg 300w, https://cytologicsbio.com/wp-content/uploads/2022/10/Types-of-Monocytes-768x597.jpg 768w, https://cytologicsbio.com/wp-content/uploads/2022/10/Types-of-Monocytes.jpg 1430w" sizes="(max-width: 1024px) 100vw, 1024px" /></figure>
  956.  
  957.  
  958.  
  959. <div class="wp-block-spacer" style="height: 16px;" aria-hidden="true"> </div>
  960.  
  961.  
  962.  
  963. <h2 class="wp-block-heading">Research and Therapeutic Applications of CD14+ Monocytes</h2>
  964.  
  965.  
  966.  
  967. <p style="font-size: 18px;">There are multiple and diverse uses of CD14+ monocytes in research and medicine, which are discussed below:</p>
  968.  
  969.  
  970.  
  971. <h3 class="wp-block-heading">1. Neuroprotective effects of CD14+ monocytes</h3>
  972.  
  973.  
  974.  
  975. <p style="font-size: 18px;">CD14+ monocytes are considered a critical cell type in treating hypoxic-ischemic (HI) brain injuries using cord-blood mononuclear cells. Researchers from Duke University found that umbilical cord blood CD14+ monocytes possess several secretory proteins with solid potential to protect neurons. They efficiently <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218906" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">prevented neuronal cell death and decreased glial activation</span></mark></a> due to oxygen and glucose deprivation.<sup>[<a href="#references">6</a>]</sup></p>
  976.  
  977.  
  978.  
  979. <h3 class="wp-block-heading">2. Tissue repairment and healing</h3>
  980.  
  981.  
  982.  
  983. <p style="font-size: 18px;">CD14+ monocytes have been studied for their tissue healing properties. A study using freshly extracted circulating CD14+ monocytes in diabetic mice revealed that <a href="https://www.ahajournals.org/doi/full/10.1161/01.ATV.0000203513.29227.6f" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">CD14+ cells alleviated the deleterious effects of diabetes</span></mark></a> and promoted muscle healing and angiogenesis (vascular growth). These implications suggest a potential therapeutic role of CD14+ monocytes for diabetics.<sup>[<a href="#references">7</a>]</sup></p>
  984.  
  985.  
  986.  
  987. <h3 class="wp-block-heading">3. Diagnosis of disease</h3>
  988.  
  989.  
  990.  
  991. <p style="font-size: 18px;"><em><span style="text-decoration: underline;">Early diagnosis of rheumatoid arthritis</span></em>. CD14+ monocytes isolated from rheumatoid arthritis patients <a href="https://onlinelibrary.wiley.com/doi/full/10.1002/cti2.1237" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">exhibit distinct metabolic and inflammatory phenotypes</span></mark></a> featuring over-expression of chemokines/cytokines, changes in mitochondrial morphology, and enhanced production of glycolytic enzymes compared to healthy controls. This inflammatory phenotype appears before the clinical manifestations of rheumatoid arthritis. Therefore, it can help in the early diagnosis of the disease.<sup>[<a href="#references">8</a>]</sup></p>
  992.  
  993.  
  994.  
  995. <p style="font-size: 18px;"><em><span style="text-decoration: underline;">Cancer</span>.</em> Cancer development leads to changes in the expression pattern of several molecular factors present in CD14+ monocytes. PDL-1 or programmed death one ligand is expressed in CD14+ monocytes of hepatocellular carcinoma patients’ blood and <a href="https://www.mdpi.com/2072-6694/12/8/2286" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">tends to suppress anti-tumor activities</span></mark></a> by the host immune system. A recent study indicated that the expression varies according to the stages of the tumor. Thus, this molecular marker can be evaluated in hepatocellular patients&#8217; CD14+ monocytes to assess cancer progression.<sup>[<a href="#references">9</a>]</sup></p>
  996.  
  997.  
  998.  
  999. <h3 class="wp-block-heading">4. Toxicology</h3>
  1000.  
  1001.  
  1002.  
  1003. <p style="font-size: 18px;">Environmental toxins such as cadmium are found to modulate the human immune system and influence the development of CD14+ monocytes. Researchers found that <a href="https://www.sciencedirect.com/science/article/pii/S0147651320317176" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">increased cadmium exposure</span></mark></a> decreases the number of monocytes. Therefore, CD14+ cell count can be used as an early sign of environmental exposure to cadmium.<sup>[<a href="#references">10</a>]</sup></p>
  1004.  
  1005.  
  1006.  
  1007. <h2 class="wp-block-heading">Summary</h2>
  1008.  
  1009.  
  1010.  
  1011. <p style="font-size: 18px;">Monocytes are an important component of the innate immune system that develop from the bone marrow. They are the precursors of macrophages. Their homeostatic functions in health and disease make them a valuable research tool.</p>
  1012.  
  1013.  
  1014.  
  1015. <p style="font-size: 18px;">This article provided a brief explanation of their primary function and some of their research applications. New discoveries are made almost daily that are expanding our knowledge of the role monocytes play in therapeutics, diagnostics and toxicology.</p>
  1016.  
  1017.  
  1018.  
  1019. <p style="font-size: 18px;">If you’re interested in learning more on this topic, then check out some of our <a href="https://cytologicsbio.com/tag/cell-biology/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">recent blog posts</span></mark></a> on research involving immune cells and the development of new immunotherapies.</p>
  1020.  
  1021.  
  1022. <div class="wp-block-image">
  1023. <figure class="aligncenter size-large is-resized"><a href="https://blog.feedspot.com/biotech_blogs/" target="_blank" rel="noopener"><img decoding="async" class="wp-image-15741" src="https://cytologicsbio.com/wp-content/uploads/2021/04/Feedspot-Top-25-in-Biotech-1024x263.jpg" alt="Follow Us on Feedspot" width="333" height="86" srcset="https://cytologicsbio.com/wp-content/uploads/2021/04/Feedspot-Top-25-in-Biotech-1024x263.jpg 1024w, https://cytologicsbio.com/wp-content/uploads/2021/04/Feedspot-Top-25-in-Biotech-600x154.jpg 600w, https://cytologicsbio.com/wp-content/uploads/2021/04/Feedspot-Top-25-in-Biotech-300x77.jpg 300w, https://cytologicsbio.com/wp-content/uploads/2021/04/Feedspot-Top-25-in-Biotech-768x197.jpg 768w, https://cytologicsbio.com/wp-content/uploads/2021/04/Feedspot-Top-25-in-Biotech.jpg 1220w" sizes="(max-width: 333px) 100vw, 333px" /></a></figure></div>
  1024.  
  1025.  
  1026. <div id="references" class="wp-block-ps2id-block-target"> </div>
  1027.  
  1028.  
  1029. <hr class="wp-block-separator has-text-color has-black-color has-alpha-channel-opacity has-black-background-color has-background is-style-default" />
  1030.  
  1031.  
  1032. <h2 class="wp-block-heading">References</h2>
  1033.  
  1034.  
  1035.  
  1036. [1] Yáñez A, Coetzee SG, Olsson A, Muench DE, Berman BP, Hazelett DJ, et al. Granulocyte-monocyte progenitors and monocyte-dendritic cell progenitors independently produce functionally distinct monocytes. Immunity. 2017;47(5):890-902.<br /><br /></p>
  1037.  
  1038.  
  1039.  
  1040. [2] Prinyakupt J, Pluempitiwiriyawej C. Segmentation of white blood cells and comparison of cell morphology by linear and naïve Bayes classifiers. Biomedical engineering online. 2015;14(1):1-19.<br /><br /></p>
  1041.  
  1042.  
  1043.  
  1044. [3] Kapellos TS, Bonaguro L, Gemünd I, Reusch N, Saglam A, Hinkley ER, et al. Human monocyte subsets and phenotypes in major chronic inflammatory diseases. Frontiers in immunology. 2019:2035.<br /><br /></p>
  1045.  
  1046.  
  1047.  
  1048. [4] Wacleche VS, Tremblay CL, Routy J-P, Ancuta P. The biology of monocytes and dendritic cells: contribution to HIV pathogenesis. Viruses. 2018;10(2):65.<br /><br /></p>
  1049.  
  1050.  
  1051.  
  1052. [5] Levy E, Xanthou G, Petrakou E, Zacharioudaki V, Tsatsanis C, Fotopoulos S, et al. Distinct roles of TLR4 and CD14 in LPS-induced inflammatory responses of neonates. Pediatric research. 2009;66(2):179-84.<br /><br /></p>
  1053.  
  1054.  
  1055.  
  1056. [6] Saha A, Patel S, Xu L, Scotland P, Schwartzman J, Filiano AJ, et al. Human umbilical cord blood monocytes, but not adult blood monocytes, rescue brain cells from hypoxic-ischemic injury: Mechanistic and therapeutic implications. PloS one. 2019;14(9):e0218906.<br /><br /></p>
  1057.  
  1058.  
  1059.  
  1060. [7] Awad O, Dedkov EI, Jiao C, Bloomer S, Tomanek RJ, Schatteman GC. Differential healing activities of CD34+ and CD14+ endothelial cell progenitors. Arteriosclerosis, thrombosis, and vascular biology. 2006;26(4):758-64.<br /><br /></p>
  1061.  
  1062.  
  1063.  
  1064. [8] McGarry T, Hanlon MM, Marzaioli V, Cunningham CC, Krishna V, Murray K, et al. Rheumatoid arthritis CD14+ monocytes display metabolic and inflammatory dysfunction, a phenotype that precedethe s clinical manifestation of disease. Clinical &amp; translational immunology. 2021;10(1):e1237.<br /><br /></p>
  1065.  
  1066.  
  1067.  
  1068. [9] Asai A, Yasuoka H, Matsui M, Tsuchimoto Y, Fukunishi S, Higuchi K. Programmed Death 1 Ligand Expression in the Monocytes of Patients with Hepatocellular Carcinoma Depends on Tumor Progression. Cancers. 2020;12(8):2286.<br /><br /></p>
  1069.  
  1070.  
  1071.  
  1072. [10] Lu Y, Wu J, Gu W, Huang Z, Shu Z, Huang M, et al. Single-cell transcriptomics uncovers phenotypic alterations in the monocytes in a Chinese population with chronic cadmium exposure. Ecotoxicology and Environmental Safety. 2021;211:111881.<br /><br /></p>
  1073. ]]></content:encoded>
  1077. </item>
  1078. <item>
  1079. <title>Neoantigen T-Cell Receptor Gene Therapy for Pancreatic Cancer Shows Promise in Clinical Trial</title>
  1080. <link>https://cytologicsbio.com/neoantigen-t-cell-receptor-gene-therapy-for-pancreatic-cancer-shows-promise-in-clinical-trial/</link>
  1082. <dc:creator><![CDATA[Cytologics]]></dc:creator>
  1083. <pubDate>Mon, 08 Aug 2022 02:40:55 +0000</pubDate>
  1084. <category><![CDATA[News]]></category>
  1085. <category><![CDATA[Scientific Knowledge]]></category>
  1086. <category><![CDATA[Cell Therapy]]></category>
  1087. <category><![CDATA[Gene Therapy]]></category>
  1088. <category><![CDATA[T cells]]></category>
  1089. <guid isPermaLink="false">https://cytologicsbio.com/?p=54032</guid>
  1090.  
  1091. <description><![CDATA[Cancer immunotherapy is at the leading edge of personalized medicine. Immunotherapy for patients with cancer involves the use of immune [&#8230;]]]></description>
  1092. <content:encoded><![CDATA[
  1093. <p style="font-size: 18px;">Cancer immunotherapy is at the leading edge of personalized medicine. Immunotherapy for patients with cancer involves the use of immune cells, often the patient’s own cells, to develop a treatment to target tumor cells. The two most widely studied cancer immunotherapies have been <a href="https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-02006-4" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">tumor-infiltrating lymphocyte (or TIL) therapies</span></mark></a> and <a href="https://cytologicsbio.com/recent-developments-made-in-car-t-cell-therapies/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">chimeric antigen receptor (CAR) T-cell therapies.</span></mark></a> Despite the promising outcomes for some patients treated with these approaches, some forms of cancer, such as pancreatic cancer, seem resistant.</p>
  1094.  
  1095.  
  1096.  
  1097. <p style="font-size: 18px;">Pancreatic ductal adenocarcinoma is one of the most challenging cancers to treat and has a high mortality rate. A collaboration of scientists from Earle A. Chiles Research Institute of the Providence Cancer Institute and the National Cancer Institute previously <a href="https://pubmed.ncbi.nlm.nih.gov/35648703/" target="_blank" rel="noreferrer noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">identified T-cell receptors that target KRAS G12D,</span></mark></a> a &#8220;hot spot&#8221; signaling protein mutation found in certain cancers.<sup>[<a href="#references">1</a>]</sup> Clinical researchers in this collaboration developed autologous TILs to treat a colorectal cancer patient which led to regression of metastases.</p>
  1098.  
  1099.  
  1100.  
  1101. <p style="font-size: 18px;">The finding that pancreatic cancers also have <a href="https://www.nature.com/articles/s41467-021-24562-2" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;"><em>KRAS</em> mutations</span></mark></a> led the research group to explore whether T-cell receptor gene therapy that targets mutant KRAS proteins (neoantigens), could provide a positive therapeutic response for patients with pancreatic cancer as well.<sup>[<a href="#references">2</a>]</sup></p>
  1102.  
  1103.  
  1104.  
  1105. <p style="font-size: 18px;">A clinical trial was conducted in a single patient with pancreatic cancer that had metastasized to the lungs. Peripheral blood mononuclear cells (PBMCs) were collected from the patient as the first step in creating the immunotherapy. To engineer T cells targeting mutant KRAS protein, T-cell receptors were isolated from the previously treated patient with colorectal cancer, synthesized, and cloned for use to transduce the PBMCs. T cells were isolated from the transduced PBMCs, expanded in culture, and harvested for patient administration. </p>
  1106.  
  1107.  
  1108.  
  1109. <p style="font-size: 18px;">The patient received one infusion of the genetically engineered autologous T cells (85% <a href="https://cytologicsbio.com/product/cd8-cytotoxic-t-cells/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">CD8+ T cells</span></mark></a> and 15% <a href="https://cytologicsbio.com/product/cd4-helper-t-cells/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">CD4+ T cells</span></mark></a>). Over 90% of the cells expressed the mutant KRAS neoantigen–specific T-cell receptors. Although the patient experienced short-lived toxic events associated with the preconditioning therapy that was provided days before the T-cell infusion, no adverse effects were seen with the engineered T cells.</p>
  1110.  
  1111.  
  1112.  
  1113. <figure class="wp-block-image aligncenter size-full"><img decoding="async" width="459" height="292" class="wp-image-54080" src="https://cytologicsbio.com/wp-content/uploads/2022/08/Mutant-KRAS-G12D-peptide.jpg" alt="Engineered t-cell recognizing mutant KRAS G12D peptide" srcset="https://cytologicsbio.com/wp-content/uploads/2022/08/Mutant-KRAS-G12D-peptide.jpg 459w, https://cytologicsbio.com/wp-content/uploads/2022/08/Mutant-KRAS-G12D-peptide-300x191.jpg 300w" sizes="(max-width: 459px) 100vw, 459px" />
  1114. <figcaption>Figure 1. Pancreatic Cancer may be vulnerable to engineered T cells that recognize a “hot-spot” mutation called KRAS G12D.</figcaption>
  1115. </figure>
  1116.  
  1117.  
  1118.  
  1119. <p style="font-size: 18px;">A month after the T-cell infusion, computed tomography scans showed regression of metastatic lung lesions, and the partial response (a reduction in the size of a tumor by 50% or more) was determined to be 62%. Tumor regression was still noted by the 6-month follow up with an overall partial response of 72%.</p>
  1120.  
  1121.  
  1122.  
  1123. <p style="font-size: 18px;">Treatment of a second patient with engineered T-cells, but with a modification in the preconditioning protocol, had a less favorable outcome. The exact reason for this is unknown, but the approach remains promising.</p>
  1124.  
  1125.  
  1126.  
  1127. <p style="font-size: 18px;">The research data obtained in these one-patient clinical trials warrant additional studies with more participants to determine the efficacy and safety of neoantigen T-cell receptor gene therapy for pancreatic and other mutant KRAS–expressing cancers. The approach could also be adapted to engineer cells targeting other tumor specific neoantigens that may be more important in a given cancer.</p>
  1128.  
  1129.  
  1130.  
  1131. <h2 class="wp-block-heading">Want to Learn More?</h2>
  1132.  
  1133.  
  1134.  
  1135. <p style="font-size: 18px;">To learn more on this topic, check out our recent articles on emerging <a href="https://cytologicsbio.com/tag/cell-therapy/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">cell &amp; gene therapies</span></mark></a> and <a href="https://cytologicsbio.com/recent-breakthroughs-in-off-the-shelf-nk-cells-for-cancer-immunotherapy/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">cancer research.</span></mark></a> You can also subscribe to our blog by entering your email below for industry updates, technical articles and scientific case studies.</p>
  1136.  
  1137.  
  1138.  
  1139.  
  1140. <script>
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  1153.  
  1154.  
  1155. <div class="wp-block-spacer" style="height: 30px;" aria-hidden="true"> </div>
  1156.  
  1157.  
  1158.  
  1159. <div id="references" class="wp-block-ps2id-block-target"> </div>
  1160.  
  1161.  
  1162. <hr class="wp-block-separator has-alpha-channel-opacity is-style-default" />
  1163.  
  1164.  
  1165. <h2 class="wp-block-heading">References</h2>
  1166.  
  1167.  
  1168.  
  1169. [1] Leidner R, Sanjuan Silva N, Huang H, Sprott D, Zheng C, Shih YP, Leung A, Payne R, Sutcliffe K, Cramer J, Rosenberg SA, Fox BA, Urba WJ, Tran E. Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer. N Engl J Med. 2022 Jun 2;386(22):2112-2119. doi: 10.1056/NEJMoa2119662. PMID: 35648703.</p>
  1170.  
  1171.  
  1172.  
  1173. [2] Bear, A.S., Blanchard, T., Cesare, J. et al. Biochemical and functional characterization of mutant KRAS epitopes validates this oncoprotein for immunological targeting. Nat Commun 12, 4365 (2021). https://doi.org/10.1038/s41467-021-24562-2.</p>
  1174. ]]></content:encoded>
  1178. </item>
  1179. <item>
  1180. <title>[VIDEO] How to Thaw PBMCs for Maximum Cell Viability and Recovery</title>
  1181. <link>https://cytologicsbio.com/video-how-to-thaw-pbmcs-for-maximum-cell-viability-and-recovery/</link>
  1183. <dc:creator><![CDATA[Cytologics]]></dc:creator>
  1184. <pubDate>Fri, 05 Aug 2022 01:07:51 +0000</pubDate>
  1185. <category><![CDATA[Technical Resources]]></category>
  1186. <category><![CDATA[Video]]></category>
  1187. <category><![CDATA[Cryopreserved]]></category>
  1188. <category><![CDATA[PBMC]]></category>
  1189. <category><![CDATA[Tips & Tricks]]></category>
  1190. <guid isPermaLink="false">https://cytologicsbio.com/?p=53744</guid>
  1191.  
  1192. <description><![CDATA[In this video, we will demonstrate how to thaw peripheral blood mononuclear cells,or PBMCs, for maximum cell viability and recovery. [&#8230;]]]></description>
  1193. <content:encoded><![CDATA[
  1194. <p><iframe title="YouTube video player" src="https://www.youtube.com/embed/mI9ROwZuRsU" width="560" height="315" frameborder="0" allowfullscreen="allowfullscreen"></iframe></p>
  1195.  
  1196.  
  1197.  
  1198. <div class="wp-block-spacer" style="height: 30px;" aria-hidden="true"> </div>
  1199.  
  1200.  
  1201.  
  1202. <p style="font-size: 18px;">In this video, we will demonstrate how to thaw <a href="https://cytologicsbio.com/product/peripheral-blood-mononuclear-cells/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">peripheral blood mononuclear cells,</span></mark></a>or PBMCs, for maximum cell viability and recovery.</p>
  1203.  
  1204.  
  1205.  
  1206. <p style="font-size: 18px;">Human PBMCs are frequently used in the study of biological processes and drug development, and for applications such as <em>in vitro</em> cell-based assays.</p>
  1207.  
  1208.  
  1209.  
  1210. <p style="font-size: 18px;">Fresh PBMCs are often cryopreserved and stored in liquid nitrogen if they are not needed immediately for research applications. Researchers with limited access to donors or ability to isolate immune cells from whole blood may purchase ready-to-use, cryopreserved PBMCs from biospecimen suppliers like Cytologics.</p>
  1211.  
  1212.  
  1213.  
  1214. <div class="wp-block-buttons is-content-justification-center is-layout-flex wp-container-core-buttons-is-layout-9 wp-block-buttons-is-layout-flex">
  1215. <div class="wp-block-button has-custom-font-size" style="font-size: 18px;"><a class="wp-block-button__link has-white-color has-luminous-vivid-orange-background-color has-text-color has-background" href="https://cytologicsbio.com/should-you-order-fresh-or-cryopreserved-pbmcs/"><strong>RELATED: Using Fresh vs. Cryopreserved PBMCs</strong></a></div>
  1216. </div>
  1217.  
  1218.  
  1219.  
  1220. <div class="wp-block-spacer" style="height: 30px;" aria-hidden="true"> </div>
  1221.  
  1222.  
  1223.  
  1224. <p style="font-size: 18px;">Proper handling and thawing of these cells is critical for obtaining optimal viability and recovery. This instructional video covers best practices for thawing PBMCs prior to use in downstream applications.</p>
  1225.  
  1226.  
  1227.  
  1228. <p style="font-size: 18px;">In addition, we&#8217;ve included our protocol to thaw PBMCs protocol using RPMI medium below<a href="#download"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">(PDF version available for download at the bottom of the page).</span></mark></a>As thawing protocols for specific cell types may vary, always refer to the recommended protocol received with your cells when ordering from Cytologics.</p>
  1229.  
  1230.  
  1231.  
  1232.  
  1233. <hr class="wp-block-separator has-text-color has-black-color has-css-opacity has-black-background-color has-background aligncenter is-style-wide" />
  1234.  
  1235.  
  1236. <div class="wp-block-spacer" style="height: 20px;" aria-hidden="true"> </div>
  1237.  
  1238.  
  1239.  
  1240. <h2 class="wp-block-heading">Key Reagents and Supplies</h2>
  1241.  
  1242.  
  1243.  
  1244. <ul>
  1245. <li style="line-height: 1.5; padding-bottom: 14px; font-size: 18px;">RPMI with L-Glutamine and 10% FBS</li>
  1246. <li style="line-height: 1.5; padding-bottom: 14px; font-size: 18px;">Ethanol-70%</li>
  1247. <li style="line-height: 1.5; padding-bottom: 14px; font-size: 18px;">15 mL tubes</li>
  1248. <li style="line-height: 1.5; padding-bottom: 14px; font-size: 18px;">Pipets and pipet dispenser</li>
  1249. <li style="line-height: 1.5; padding-bottom: 14px; font-size: 18px;">37℃ water bath</li>
  1250. <li style="line-height: 1.5; padding-bottom: 14px; font-size: 18px;">CO2 incubator</li>
  1251. <li style="line-height: 1.5; padding-bottom: 14px; font-size: 18px;">Centrifuge</li>
  1252. </ul>
  1253.  
  1254.  
  1255. <hr class="wp-block-separator has-text-color has-black-color has-css-opacity has-black-background-color has-background aligncenter is-style-wide" />
  1256.  
  1257.  
  1258. <div class="wp-block-spacer" style="height: 20px;" aria-hidden="true"> </div>
  1259.  
  1260.  
  1261.  
  1262. <h2 class="wp-block-heading">Steps for Thawing PBMCs</h2>
  1263.  
  1264.  
  1265.  
  1266. <p style="font-size: 16px;"><em>Note: follow all safety precautions, and ensure you have the required equipment, materials and reagents to perform the following protocol.</em></p>
  1267.  
  1268.  
  1269.  
  1270. <ol style="font-size: 18px;">
  1271. <li style="line-height: 1.5; padding-bottom: 14px;">Warm water bath to 37℃, and ensure RPMI is warmed to 37℃.</li>
  1272. <li style="line-height: 1.5; padding-bottom: 14px;">When removing frozen cells from liquid nitrogen storage, it is important to minimize exposure to room temperature (15-25°C). If not proceeding directly to thawing, place the cells on dry ice or in a liquid nitrogen container.</li>
  1273. <li style="line-height: 1.5; padding-bottom: 14px;">Place cryopreserved cell vial in 37℃ water bath. Submerge cryovial halfway and thaw for approximately 2 minutes. Gently swirl vial.</li>
  1274. <li style="line-height: 1.5; padding-bottom: 14px;">Examine vial, continue 37℃ thaw until ice just before last ice crystal has melted. Do not allow vial to warm to greater than 10℃.</li>
  1275. <li style="line-height: 1.5; padding-bottom: 14px;">Transfer vial to a biosafety cabinet and wipe the outside of the vial with 70% ethanol or isopropanol.</li>
  1276. <li style="line-height: 1.5; padding-bottom: 14px;">Pour thawed cells into 15 mL conical tube containing 5 mL of RPMI that has been pre-warmed to 37℃. Do not use a pipet for this step.</li>
  1277. <li style="line-height: 1.5; padding-bottom: 14px;">Rinse cryovial with 2 mL pre-warmed RPM using a pipet. Pour cells into 15 mL conical tube.</li>
  1278. <li style="line-height: 1.5; padding-bottom: 14px;">Incubate cells for 5 minutes at 37℃.</li>
  1279. <li style="line-height: 1.5; padding-bottom: 14px;">Centrifuge cell suspension at 260 x g at 20℃ (room temp) for 5 min, low brake.</li>
  1280. <li style="line-height: 1.5; padding-bottom: 14px;">Pour off the supernatant.</li>
  1281. <li style="line-height: 1.5; padding-bottom: 14px;">Add 2 mL pre-warmed RPMI using a pipet. Mix by flicking tube (avoid pipetting).</li>
  1282. <li style="line-height: 1.5; padding-bottom: 14px;">Incubate cell suspension for 1 hour to overnight in a 37℃ CO2 incubator. Leave cap loose so gas transfer can occur.</li>
  1283. <li style="line-height: 1.5; padding-bottom: 14px;">Cells are now ready for use in downstream applications.</li>
  1284. </ol>
  1285.  
  1286.  
  1287. <hr class="wp-block-separator has-text-color has-black-color has-css-opacity has-black-background-color has-background aligncenter is-style-wide" />
  1288.  
  1289.  
  1290. <div class="wp-block-spacer" style="height: 20px;" aria-hidden="true"> </div>
  1291.  
  1292.  
  1293.  
  1294. <h2 class="wp-block-heading">Related Resources</h2>
  1295.  
  1296.  
  1297.  
  1298. <div id="download" class="wp-block-ps2id-block-target"> </div>
  1299.  
  1300.  
  1301.  
  1302. <div class="wp-block-columns is-layout-flex wp-container-core-columns-is-layout-3 wp-block-columns-is-layout-flex">
  1303. <div class="wp-block-column is-layout-flow wp-block-column-is-layout-flow" style="flex-basis: 80%;">
  1304. <p style="font-size: 18px;">Interested in learning more on this topic? Then check out this <a href="https://cytologicsbio.com/pbmc-thawing-protocol-how-to-optimize-cell-recovery/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;"><strong>related content on thawing primary cells,</strong></span></mark></a>including a protocol for using culture media types other than RPMI (such as <a href="https://www.labome.com/method/Cell-Culture-Media-A-Review.html" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">IMDM or DMEM</span></mark></a>).</p>
  1305.  
  1306.  
  1307.  
  1308. <p style="font-size: 18px;">Also, click the link below to download a free protocol for thawing PBMCs as demonstrated in the video to keep with you in the lab!</p>
  1309. </div>
  1310.  
  1311.  
  1312.  
  1313. <div class="wp-block-column is-layout-flow wp-block-column-is-layout-flow" style="flex-basis: 33.33%;">
  1314. <figure class="wp-block-image size-full is-resized"><a href="https://cytologicsbio.com/wp-content/uploads/2022/08/Cytologics-PBMC-Thawing-Protocol.pdf" target="_blank" rel="noreferrer noopener"><img decoding="async" class="wp-image-53982" src="https://cytologicsbio.com/wp-content/uploads/2022/08/Cytologics-Protocol-Graphic.jpg" alt="" width="147" height="201" srcset="https://cytologicsbio.com/wp-content/uploads/2022/08/Cytologics-Protocol-Graphic.jpg 306w, https://cytologicsbio.com/wp-content/uploads/2022/08/Cytologics-Protocol-Graphic-219x300.jpg 219w" sizes="(max-width: 147px) 100vw, 147px" /></a></figure>
  1315. </div>
  1316. </div>
  1317.  
  1318.  
  1319.  
  1320. <div class="wp-block-buttons is-content-justification-center is-layout-flex wp-container-core-buttons-is-layout-10 wp-block-buttons-is-layout-flex">
  1321. <div class="wp-block-button has-custom-font-size" style="font-size: 18px;"><a class="wp-block-button__link has-luminous-vivid-orange-background-color has-background" href="https://cytologicsbio.com/wp-content/uploads/2022/08/Cytologics-PBMC-Thawing-Protocol.pdf"><strong>Download PBMC Thawing Protocol</strong></a></div>
  1322. </div>
  1323.  
  1324.  
  1325.  
  1326. <div class="wp-block-spacer" style="height: 20px;" aria-hidden="true"> </div>
  1327. ]]></content:encoded>
  1331. </item>
  1332. <item>
  1333. <title>How NK Cells Crosstalk with Other Innate Immune Cells</title>
  1334. <link>https://cytologicsbio.com/how-nk-cells-crosstalk-with-other-innate-immune-cells/</link>
  1336. <dc:creator><![CDATA[Cytologics]]></dc:creator>
  1337. <pubDate>Mon, 20 Jun 2022 03:54:38 +0000</pubDate>
  1338. <category><![CDATA[Scientific Knowledge]]></category>
  1339. <category><![CDATA[Cell Biology]]></category>
  1340. <category><![CDATA[Immunology]]></category>
  1341. <category><![CDATA[NK Cells]]></category>
  1342. <guid isPermaLink="false">https://cytologicsbio.com/?p=52134</guid>
  1343.  
  1344. <description><![CDATA[Natural killer (NK) cells are a type of lymphocyte that spontaneously respond to stressed cells without any earlier exposure to [&#8230;]]]></description>
  1345. <content:encoded><![CDATA[
  1346. <p style="font-size: 18px;">Natural killer (NK) cells are a type of lymphocyte that spontaneously respond to stressed cells without any earlier exposure to an antigen by using their <a href="https://openarchive.ki.se/xmlui/handle/10616/46780" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">germline-encoded receptors.</span></mark></a><sup><a href="#references">[1]</a></sup> NK cells are an important arm of the innate immune system and exert their effector functions as a standalone cell or in combination with other immune cells. They eliminate a range of cellular targets such as stressed, viral-infected, and cancer transformed cells.</p>
  1347.  
  1348.  
  1349.  
  1350. <p style="font-size: 18px;">NK cells are directly activated by different molecular signals generated by stimulatory and inhibitory receptors from macrophages, dendritic cells (DCs), eosinophils and T cells. This co-stimulation, or &#8220;crosstalk,&#8221; leads to NK cell activation and regulation of other innate and adaptive immune responses.</p>
  1351.  
  1352.  
  1353.  
  1354. <p style="font-size: 18px;">In this article, we will examine NK cell crosstalk with various immune cells and the <a href="https://www.futuremedicine.com/doi/abs/10.2217/imt.11.102" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">associated signaling pathways.</span></mark></a><sup><a href="#references">[2]</a></sup></p>
  1355.  
  1356.  
  1357.  
  1358.  
  1359.  
  1360. <h2 class="wp-block-heading">NK Cells Crosstalk with Dendritic Cells and T cells</h2>
  1361.  
  1362.  
  1363.  
  1364. <p style="font-size: 18px;">The crosstalk between dendritic cells and NK cells plays a crucial role in triggering immune responses against several targets. This interaction works bi-directionally and greatly influences the subsequent adaptive immune responses.</p>
  1365.  
  1366.  
  1367.  
  1368. <p style="font-size: 18px;">Scientists from Gustave Roussy in France found that the <a href="https://pubmed.ncbi.nlm.nih.gov/11956017/" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">pre-activation of NK cells by DCs</span></mark></a> is imperative for an effective immune response against tumors both in-vitro and in-vivo.<sup><a href="#references">[3]</a></sup> The same observation has been corroborated for viral infections.<sup><a href="#references">[4,5]</a></sup> Moreover, pattern recognition receptors (PRRs) of the innate immune system such as toll-like receptors (TLR) signaling participate in this DC-NK cross-talk by triggering the maturation of DCs and the secretion of various synergistic cytokines that subsequently activate NK cells.</p>
  1369.  
  1370.  
  1371.  
  1372. <p style="font-size: 18px;">Interaction of NK cells with immature dendritic cells (DCs) results in reciprocal activation as shown in the figure below. Mature DCs release IL-12 that efficiently promotes the secretion of IFN-γ by NK cells. The further secretion of IL-18 enhances the IL-12 effect by inducing IL-12 receptor on the surface of NK cells. Furthermore, <a href="https://ashpublications.org/blood/article/112/5/1776/25447/Human-natural-killer-cells-exposed-to-IL-2-IL-12" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">IL-18 and IL-12 work synergistically</span></mark></a> to increase the cytolytic activity of NK cells and promote the polarization of Th1.<sup><a href="#references">[6,7]</a></sup> Upon activation, NK cells secrete more cytokines i.e., TNF and IFN-γ, that increase the maturation of DCs.</p>
  1373.  
  1374.  
  1375.  
  1376. <p style="font-size: 18px;">TNF consequently enhances the induction of co-stimulatory molecules on the surface of dendritic cells and synergizes with IFN-γ to trigger IL-12 production by DCs that works along with other cytokines to perform different functions as described earlier.<sup><a href="#references">[8,9]</a></sup> Further, IFN-γ induces the expression of IL-15 on the membrane of DCs that in turn helps in maintaining the survival and activation of both NK and <a href="https://cytologicsbio.com/understanding-the-use-of-t-cells-in-immunology-research/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">T cells.</span></mark></a><sup><a href="#references">[10]</a></sup> This loop continues and results in an improved innate immune response.</p>
  1377.  
  1378.  
  1379.  
  1380. <h3 class="wp-block-heading">Figure 1. Crosstalk between NK Cells and Dendritic Cells</h3>
  1381.  
  1382.  
  1383.  
  1384. <figure class="wp-block-image size-large"><img decoding="async" width="1024" height="652" class="wp-image-52135" src="https://cytologicsbio.com/wp-content/uploads/2022/05/Cross-talk-between-NK-cells-and-Dentritic-Cells-1024x652.png" alt="" srcset="https://cytologicsbio.com/wp-content/uploads/2022/05/Cross-talk-between-NK-cells-and-Dentritic-Cells-1024x652.png 1024w, https://cytologicsbio.com/wp-content/uploads/2022/05/Cross-talk-between-NK-cells-and-Dentritic-Cells-600x382.png 600w, https://cytologicsbio.com/wp-content/uploads/2022/05/Cross-talk-between-NK-cells-and-Dentritic-Cells-300x191.png 300w, https://cytologicsbio.com/wp-content/uploads/2022/05/Cross-talk-between-NK-cells-and-Dentritic-Cells-768x489.png 768w, https://cytologicsbio.com/wp-content/uploads/2022/05/Cross-talk-between-NK-cells-and-Dentritic-Cells.png 1430w" sizes="(max-width: 1024px) 100vw, 1024px" /></figure>
  1385.  
  1386.  
  1387.  
  1388. <h2 class="wp-block-heading">Crosstalk between Macrophages and NK Cells</h2>
  1389.  
  1390.  
  1391.  
  1392. <p style="font-size: 18px;"><a href="https://www.frontiersin.org/articles/10.3389/fimmu.2012.00403/full" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">Macrophages activate NK cells</span></mark></a> either by soluble mediators or cytokines i.e., IL-12 and IL-18, or by direct cell to cell connections.<sup><a href="#references">[11]</a></sup> Following a microbial infection, macrophages release several proinflammatory cytokines that activate NK cells including IL-18, IL-12, TNF-alpha, CCR7, and type I interferon.</p>
  1393.  
  1394.  
  1395.  
  1396. <p style="font-size: 18px;">Moreover, the polarization of naïve M0 and anti-inflammatory macrophages M2 to the proinflammatory macrophages M1 enhances the activation of NK cells resulting in an intense proinflammatory response.</p>
  1397.  
  1398.  
  1399.  
  1400. <p style="font-size: 18px;">As a result, stimulated NK cells eradicate other cells that express low MHC levels on their membrane such as virally infected cells and tumor cells. NK cells can also regulate the inflammatory response by inhibiting M1 in the presence of IL-10.<sup><a href="#references">[12,13]</a></sup></p>
  1401.  
  1402.  
  1403.  
  1404. <h2 class="wp-block-heading">Research Implications of NK Cell Crosstalk with Other Immune Cells</h2>
  1405.  
  1406.  
  1407.  
  1408. <h3 class="wp-block-heading">Co-culturing of Immune Cells</h3>
  1409.  
  1410.  
  1411.  
  1412. <p style="font-size: 18px;">The crosstalk between NK cells with other immune cells can be effectively used in research to study the molecular signaling of the innate immune response and gain insight into cell-cell interactions using <strong>“cells co-culture.”</strong></p>
  1413.  
  1414.  
  1415.  
  1416. <p style="font-size: 18px;">Research has shown that the co-culture of NK cells and monocytes or macrophages <a href="https://www.jimmunol.org/content/173/10/6418" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">upregulated the expression of CD69</span></mark></a> in NK cells that in turn activates them.<sup><a href="#references">[14-16]</a></sup> The activation occurs due to cell-cell contact and causes NK cells to release IFN-γ.<sup><a href="#references">[14,17]</a></sup> Thus, it can help mediate different cellular and therapeutic functions.</p>
  1417.  
  1418.  
  1419.  
  1420. <h3 class="wp-block-heading">Cancer Immunotherapy</h3>
  1421.  
  1422.  
  1423.  
  1424. <p style="font-size: 18px;">Research reported that co-culturing of NK cells and dendritic cells helps DCs to mature and release IL-12 and TNF as well as increases the levels of other costimulatory ligands i.e., CD86.<sup><a href="#references">[18]</a></sup> IL-12 mediate NK cells activation and these NK cells can serve as <a href="https://pubmed.ncbi.nlm.nih.gov/11422197/" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">effective immunotherapy against cancer.</span></mark></a><sup><a href="#references">[19]</a></sup></p>
  1425.  
  1426.  
  1427. <div class="wp-block-image">
  1428. <figure class="aligncenter size-large is-resized"><a href="https://cytologicsbio.com/natural-killer-cells-cell-biology-and-research-applications/"><img decoding="async" class="wp-image-52714" src="https://cytologicsbio.com/wp-content/uploads/2022/06/NK-Cells-Basic-Biology-and-Research-Applications-1024x449.jpg" alt="NK Cells attacking cancer cell" width="640" height="281" srcset="https://cytologicsbio.com/wp-content/uploads/2022/06/NK-Cells-Basic-Biology-and-Research-Applications-1024x449.jpg 1024w, https://cytologicsbio.com/wp-content/uploads/2022/06/NK-Cells-Basic-Biology-and-Research-Applications-600x263.jpg 600w, https://cytologicsbio.com/wp-content/uploads/2022/06/NK-Cells-Basic-Biology-and-Research-Applications-300x132.jpg 300w, https://cytologicsbio.com/wp-content/uploads/2022/06/NK-Cells-Basic-Biology-and-Research-Applications-768x337.jpg 768w, https://cytologicsbio.com/wp-content/uploads/2022/06/NK-Cells-Basic-Biology-and-Research-Applications-1536x673.jpg 1536w, https://cytologicsbio.com/wp-content/uploads/2022/06/NK-Cells-Basic-Biology-and-Research-Applications-scaled.jpg 2048w" sizes="(max-width: 640px) 100vw, 640px" /></a></figure></div>
  1429.  
  1430.  
  1431. <h3 class="wp-block-heading">Viral Infections</h3>
  1432.  
  1433.  
  1434.  
  1435. <p style="font-size: 18px;">Recent research has provided evidence that NK and DCs crosstalk is compromised during HIV-1 infection. <a href="https://www.researchgate.net/publication/6793563_Characterization_of_the_defective_interaction_between_a_subset_of_natural_killer_cells_and_dendritic_cells_in_HIV-1_infection" target="_blank" rel="noopener"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">This defective cell communication</span></mark></a> involves abnormalities in the process of CD56<sup>neg</sup> NK cell activation through DCs and DCs maturation.<sup><a href="#references">[20]</a></sup> Other molecular mechanisms involved in this crosstalk can be targeted and studied using co-culture. The combination of NK-DC immunotherapy can be a promising cellular therapy in improving the immune functions in HIV-1 infection.</p>
  1436.  
  1437.  
  1438.  
  1439. <h2 class="wp-block-heading">Conclusion</h2>
  1440.  
  1441.  
  1442.  
  1443. <p style="font-size: 18px;">Studies performed on NK cells over the past decade have clearly shown that, during immune response, NK cells act by not only displaying their own protective functions, but also interacting with other immune cells to optimize the response against pathogens.</p>
  1444.  
  1445.  
  1446.  
  1447. <p style="font-size: 18px;">NK cells crosstalk with DCs and other immune cells through complex signaling pathways that fulfill complementary tasks. Ongoing research in this field is likely to yield greater understanding of NK activation and lead to advanced therapies for cancers and other diseases.</p>
  1448.  
  1449.  
  1450.  
  1451. <h3 class="wp-block-heading">Want to Learn More?</h3>
  1452.  
  1453.  
  1454.  
  1455. <p style="font-size: 18px;">Interested to learn more basic cell biology about NK cells and their research applications? Then check our <a href="https://cytologicsbio.com/tag/nk-cells/"><mark class="has-inline-color has-vivid-cyan-blue-color" style="background-color: rgba(0, 0, 0, 0);"><span style="text-decoration: underline;">related content on NK cells</span></mark></a> or subscribe to our blog by entering your email below for industry updates, technical articles and scientific case studies.</p>
  1456.  
  1457.  
  1458.  
  1459.  
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  1472.  
  1473.  
  1474.  
  1475. <div id="references" class="wp-block-ps2id-block-target"> </div>
  1476.  
  1477.  
  1478.  
  1479. <h2 class="wp-block-heading">References</h2>
  1480.  
  1481.  
  1482.  
  1483. [1] Ganesan, S., <em>Regulation of Calcium Flux by Activating and Inhibitory Receptor Crosstalk in NK Cells</em>. 2019, Karolinska Institutet (Sweden).</p>
  1484.  
  1485.  
  1486.  
  1487. <p>&nbsp;</p>
  1488.  
  1489.  
  1490.  
  1491. [2] Malhotra, A. and A. Shanker, <em>NK cells: immune cross-talk and therapeutic implications.</em> Immunotherapy, 2011. <strong>3</strong>(10): p. 1143-1166.</p>
  1492.  
  1493.  
  1494.  
  1495. <p>&nbsp;</p>
  1496.  
  1497.  
  1498.  
  1499. [3] Fernandez, N.C., et al., <em>Dendritic cells (DC) promote natural killer (NK) cell functions: dynamics of the human DC/NK cell cross talk.</em> European cytokine network, 2002. <strong>13</strong>(1): p. 17-27.</p>
  1500.  
  1501.  
  1502.  
  1503. <p>&nbsp;</p>
  1504.  
  1505.  
  1506.  
  1507. [4] Lucas, M., et al., <em>Natural killer cell-mediated control of infections requires production of interleukin 15 by type I IFN-triggered dendritic cells.</em> Immunity, 2007. <strong>26</strong>(4): p. 503.</p>
  1508.  
  1509.  
  1510.  
  1511. <p>&nbsp;</p>
  1512.  
  1513.  
  1514.  
  1515. [5] Kassim, S.H., et al., <em>In vivo ablation of CD11c-positive dendritic cells increases susceptibility to herpes simplex virus type 1 infection and diminishes NK and T-cell responses.</em> Journal of virology, 2006. <strong>80</strong>(8): p. 3985-3993.</p>
  1516.  
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