{"id":62851,"date":"2026-04-29T00:31:19","date_gmt":"2026-04-28T22:31:19","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/04\/29\/tumor-derived-complement-c3-overexpression-in-stk11-mutant-lung-adenocarcinoma-drives-tumor-growth-and-immune-checkpoint-inhibitor-resistance\/"},"modified":"2026-04-29T00:31:19","modified_gmt":"2026-04-28T22:31:19","slug":"tumor-derived-complement-c3-overexpression-in-stk11-mutant-lung-adenocarcinoma-drives-tumor-growth-and-immune-checkpoint-inhibitor-resistance","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/04\/29\/tumor-derived-complement-c3-overexpression-in-stk11-mutant-lung-adenocarcinoma-drives-tumor-growth-and-immune-checkpoint-inhibitor-resistance\/","title":{"rendered":"Tumor-derived complement C3 overexpression in STK11-mutant lung adenocarcinoma drives tumor growth and immune checkpoint inhibitor resistance"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 Apr 28. doi: 10.1158\/2326-6066.CIR-25-0534. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Loss-of-function STK11 mutations occur in 15-20% of lung adenocarcinomas (LUAD) and correlate with immunotherapy failure and worse survival. By integrating analysis of human tumor samples, a human LUAD cell line panel, and CCLE and TCGA datasets, we found that C3 production was increased in human STK11-mutant versus STK11-wildtype LUAD, modulated by LKB1 loss, while high C3 expression in STK11-mutant LUAD was associated with worse survival. STK11-KO in syngeneic murine LUAD tumors resulted in increased neutrophil and reduced T cell infiltration and anti-PD-1 resistance. STK11-KO tumor growth was similar in C3-\/- versus wildtype mice. In contrast, C3 deletion in STK11-KO tumors resulted in dramatic inhibition of tumor growth and enhanced sensitivity to anti-PD-1 in immunocompetent mice but had no significant effect in CD8-depleted wildtype mice or in nude mice, pointing to tumor-derived C3 promoting immune evasion. Mechanistically, STK11 loss drove tumor-derived C3 production and downstream CXCL2 and complement factor H (CFH) production that promoted immune evasion and impaired anti-PD-1 efficacy. Our results show a C3-driven signaling axis for STK11-mutant LUAD promoting immune evasion and identifies therapeutic targets to render these tumors sensitive to anti-PD-1.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42048614\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260428183118&amp;v=2.19.0.post6+133c1fe\">42048614<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-0534\">10.1158\/2326-6066.CIR-25-0534<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 Apr 28. doi: 10.1158\/2326-6066.CIR-25-0534. Online ahead of print. ABSTRACT Loss-of-function STK11 mutations occur in 15-20% of lung adenocarcinomas (LUAD) and correlate with immunotherapy failure and worse survival. By integrating analysis of human tumor samples, a human LUAD cell line panel, and CCLE and TCGA datasets, we found that C3 production was &#8230; <a title=\"Tumor-derived complement C3 overexpression in STK11-mutant lung adenocarcinoma drives tumor growth and immune checkpoint inhibitor resistance\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/04\/29\/tumor-derived-complement-c3-overexpression-in-stk11-mutant-lung-adenocarcinoma-drives-tumor-growth-and-immune-checkpoint-inhibitor-resistance\/\" aria-label=\"Read more about Tumor-derived complement C3 overexpression in STK11-mutant lung adenocarcinoma drives tumor growth and immune checkpoint inhibitor resistance\">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-62851","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\/62851","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=62851"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/62851\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=62851"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=62851"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=62851"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}