{"id":21849,"date":"2025-01-13T18:47:08","date_gmt":"2025-01-13T17:47:08","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/01\/13\/in-situ-detection-of-individual-classical-mhc-i-gene-products-in-cancer\/"},"modified":"2025-01-13T18:47:08","modified_gmt":"2025-01-13T17:47:08","slug":"in-situ-detection-of-individual-classical-mhc-i-gene-products-in-cancer","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/01\/13\/in-situ-detection-of-individual-classical-mhc-i-gene-products-in-cancer\/","title":{"rendered":"In situ detection of individual classical MHC-I gene products in cancer"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Jan 13. doi: 10.1158\/2326-6066.CIR-24-1003. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Tumor-specific HLA class I expression is required for cytotoxic T-cell elimination of cancer cells expressing tumor-associated or neo-antigens. Cancers downregulate antigen presentation to avoid adaptive immunity. The highly polymorphic nature of the genes encoding these proteins, coupled with quaternary-structure changes after formalin fixation, complicate detection by immunohistochemistry. In this study we determined recognition of 16 specific HLA-A, B and C alleles by 15 antibodies commercially available for immunohistochemical use, identifying and validating pan and specific HLA-A, B, and C antibodies, providing a validated method that can be applied to investigate HLA-A, B and C molecule-specific loss in cancer. We applied this approach to a series of breast cancers as a proof of utility, identifying differential HLA-A, B and C loss, with a higher incidence of HLA-A and B loss in hormone-driven breast cancers, HLA-B loss in HER2+ cancers, and an equal loss of all three molecules in triple-negative disease. Additionally, we found that at the protein level, HLA-A and B loss were early events prevalent in premalignant lesions, while HLA-C loss was less common throughout tumor evolution. Effective response to immunotherapies such as checkpoint inhibitors and MHC-I-targeted cancer vaccines, which hinge on the carriage of specific allele groups, require MHC-I expression on tumor cells. These findings have implications for the success of checkpoint inhibitors and vaccine strategies.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39804685\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250113124708&amp;v=2.18.0.post9+e462414\">39804685<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-1003\">10.1158\/2326-6066.CIR-24-1003<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Jan 13. doi: 10.1158\/2326-6066.CIR-24-1003. Online ahead of print. ABSTRACT Tumor-specific HLA class I expression is required for cytotoxic T-cell elimination of cancer cells expressing tumor-associated or neo-antigens. Cancers downregulate antigen presentation to avoid adaptive immunity. The highly polymorphic nature of the genes encoding these proteins, coupled with quaternary-structure changes after formalin &#8230; <a title=\"In situ detection of individual classical MHC-I gene products in cancer\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/01\/13\/in-situ-detection-of-individual-classical-mhc-i-gene-products-in-cancer\/\" aria-label=\"Read more about In situ detection of individual classical MHC-I gene products in cancer\">Read more<\/a><\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-21849","post","type-post","status-publish","format-standard","hentry","category-cancer-immunology-reserch","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/21849","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=21849"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/21849\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=21849"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=21849"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=21849"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}