{"id":59711,"date":"2026-03-26T00:59:22","date_gmt":"2026-03-25T23:59:22","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/03\/26\/reduced-tumor-control-in-males-can-result-from-impaired-cd4-t-cell-help-through-the-cd40l-cd40-pathway\/"},"modified":"2026-03-26T00:59:22","modified_gmt":"2026-03-25T23:59:22","slug":"reduced-tumor-control-in-males-can-result-from-impaired-cd4-t-cell-help-through-the-cd40l-cd40-pathway","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/03\/26\/reduced-tumor-control-in-males-can-result-from-impaired-cd4-t-cell-help-through-the-cd40l-cd40-pathway\/","title":{"rendered":"Reduced tumor control in males can result from impaired CD4+ T-cell help through the CD40L-CD40 pathway"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 Mar 25. doi: 10.1158\/2326-6066.CIR-25-1115. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Sex-based differences in cancer incidence are incompletely understood, but potential roles for the immune system are beginning to emerge. CD4+ T cells play a central role in coordinating antitumor immunity. In addition to cytokine production, CD40L expression on CD4+ T cells provides necessary helper signaling to dendritic cells that is required for the priming of cytotoxic tumor-specific CD8+ T cells. Despite these critical functions, the impact of biological sex on the CD4+ T-cell response to cancer remains unknown. Here, we demonstrate that impaired immune-mediated tumor control in male mice compared to female mice is driven by disparate CD4+ T-cell responses in a mouse model of bladder cancer. We found that CD40L expression was reduced on CD4+ T cells isolated from males via a mechanism predominantly driven by cell-intrinsic androgen receptor signaling, resulting in decreased dendritic cell licensing through CD40 within tumor-draining lymph nodes. These deficits resulted in decreased helper CD4+ T-cell frequencies and impaired CD8+ T-cell function within the male tumor microenvironment which could be rescued by targeting the CD40L-CD40 axis. Our findings identify a novel mechanism of CD4+ T cell-based sex differences in the immune response to cancer that impairs tumor control.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41880430\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260325195921&amp;v=2.19.0.post6+133c1fe\">41880430<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-1115\">10.1158\/2326-6066.CIR-25-1115<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 Mar 25. doi: 10.1158\/2326-6066.CIR-25-1115. Online ahead of print. ABSTRACT Sex-based differences in cancer incidence are incompletely understood, but potential roles for the immune system are beginning to emerge. CD4+ T cells play a central role in coordinating antitumor immunity. In addition to cytokine production, CD40L expression on CD4+ T cells provides &#8230; <a title=\"Reduced tumor control in males can result from impaired CD4+ T-cell help through the CD40L-CD40 pathway\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/03\/26\/reduced-tumor-control-in-males-can-result-from-impaired-cd4-t-cell-help-through-the-cd40l-cd40-pathway\/\" aria-label=\"Read more about Reduced tumor control in males can result from impaired CD4+ T-cell help through the CD40L-CD40 pathway\">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-59711","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\/59711","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=59711"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/59711\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=59711"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=59711"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=59711"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}