{"id":44345,"date":"2025-09-30T20:38:33","date_gmt":"2025-09-30T18:38:33","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/09\/30\/cd4-t-cells-mediate-mhc-deficient-tumor-rejection-and-endothelial-cell-reprogramming\/"},"modified":"2025-09-30T20:38:33","modified_gmt":"2025-09-30T18:38:33","slug":"cd4-t-cells-mediate-mhc-deficient-tumor-rejection-and-endothelial-cell-reprogramming","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/09\/30\/cd4-t-cells-mediate-mhc-deficient-tumor-rejection-and-endothelial-cell-reprogramming\/","title":{"rendered":"CD4+ T cells mediate MHC-deficient tumor rejection and endothelial cell reprogramming"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Sep 30. doi: 10.1158\/2326-6066.CIR-24-1342. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Low or absent expression of major histocompatibility complex (MHC) on tumor cells is a presumed mechanism of resistance to immunotherapy, but evidence for this has largely been indirect. Likewise, whether immunotherapy can be effective without tumor MHC expression is also poorly understood. Using genetically-engineered mouse tumor cells expressing the model neoantigen ovalbumin (OVA), we found that MHC class I-deficient tumor cells, but not MHC class I-sufficient tumor cells, grew progressively when injected subcutaneously into syngeneic C57BL\/6 mice. However, combination immunotherapy using agonistic anti-CD40 and dual immune checkpoint blockade (ICB) (anti-PD1 and anti-CTLA-4) was equally effective against tumors that did not express the MHC class I H-2Kb allele, MHC class II, or IFN-\u03b3 receptor across multiple pancreatic tumor lines (regardless of OVA). Moreover, CD4+ T cells, but not CD8+ T cells or perforin, were necessary to mediate immunotherapeutic responses. We excluded a role for CD4+ T cell-instructed macrophage-mediated tumor cell death but observed reprogramming of MHC class II-expressing stromal cells within the tumor after anti-CD40\/ICB treatment. These data indicate that cancer immune surveillance by T cells does not absolutely require tumor-expressed MHC class I nor CD8+ T cells but instead can facilitate a clinically relevant remodeling of endothelial cells, further underscoring tumor-extrinsic roles for CD4+ T cells as mediators of tumor rejection and durable immune memory.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41025699\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250930143831&amp;v=2.18.0.post9+e462414\">41025699<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-1342\">10.1158\/2326-6066.CIR-24-1342<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Sep 30. doi: 10.1158\/2326-6066.CIR-24-1342. Online ahead of print. ABSTRACT Low or absent expression of major histocompatibility complex (MHC) on tumor cells is a presumed mechanism of resistance to immunotherapy, but evidence for this has largely been indirect. Likewise, whether immunotherapy can be effective without tumor MHC expression is also poorly understood. &#8230; <a title=\"CD4+ T cells mediate MHC-deficient tumor rejection and endothelial cell reprogramming\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/09\/30\/cd4-t-cells-mediate-mhc-deficient-tumor-rejection-and-endothelial-cell-reprogramming\/\" aria-label=\"Read more about CD4+ T cells mediate MHC-deficient tumor rejection and endothelial cell reprogramming\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-44345","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\/44345","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"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=44345"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/44345\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=44345"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=44345"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=44345"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}