{"id":76293,"date":"2026-09-11T23:35:53","date_gmt":"2026-09-11T21:35:53","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/09\/11\/kras-g12c-inhibition-induced-enrichment-of-mhc-ihigh-immune-active-tumor-cells-directs-immune-effector-tme-development-to-augment-therapeutic-efficacy\/"},"modified":"2026-09-11T23:35:53","modified_gmt":"2026-09-11T21:35:53","slug":"kras-g12c-inhibition-induced-enrichment-of-mhc-ihigh-immune-active-tumor-cells-directs-immune-effector-tme-development-to-augment-therapeutic-efficacy","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/09\/11\/kras-g12c-inhibition-induced-enrichment-of-mhc-ihigh-immune-active-tumor-cells-directs-immune-effector-tme-development-to-augment-therapeutic-efficacy\/","title":{"rendered":"KRAS-G12C inhibition-induced enrichment of MHC-Ihigh immune-active tumor cells directs immune-effector TME development to augment therapeutic efficacy"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 Sep 11. doi: 10.1158\/2326-6066.CIR-26-0213. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Inhibition of KRASG12C (G12Ci) has shown promising clinical activity in several cancers; however, emergence of resistance is a major limitation to long-term benefit. It remains unknown how G12Ci impacts the tumor immune microenvironment and its association with resistance. We investigated the immune modulatory impact of the G12Ci sotorasib in KrasG12C\/Trp53-\/- (KP) lung and colon carcinoma models. Single-cell RNA sequencing of tumors in both models demonstrated sotorasib-induced loss of proliferative tumor cells and to the enrichment of immune-active tumor cells with elevated NF-\uf06bB and interferon signaling, and elevated MHC-I expression. These changes led to an increased proportion of effector T cells and MHC-IIhi macrophages in the tumors, and a reduced proportion of regulatory myeloid cells. Furthermore, sotorasib-resistant tumors exhibited a marked reduction of MHC-Ihigh immune-active tumor cells and immune cell type changes. Enrichment of immune-active tumor cells was associated directly with sotorasib-induced activation of NF-\uf06bB and STAT1, leading to heightened responsiveness to inflammatory cytokines and to upregulation of MHC-I and chemokine expression. These findings indicate that modulation of immune-active tumor cell populations is a key mechanism associated with G12Ci therapeutic efficacy and the development of resistance.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42726935\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260911173553&amp;v=2.20.1\">42726935<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-26-0213\">10.1158\/2326-6066.CIR-26-0213<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 Sep 11. doi: 10.1158\/2326-6066.CIR-26-0213. Online ahead of print. ABSTRACT Inhibition of KRASG12C (G12Ci) has shown promising clinical activity in several cancers; however, emergence of resistance is a major limitation to long-term benefit. It remains unknown how G12Ci impacts the tumor immune microenvironment and its association with resistance. We investigated the immune &#8230; <a title=\"KRAS-G12C inhibition-induced enrichment of MHC-Ihigh immune-active tumor cells directs immune-effector TME development to augment therapeutic efficacy\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/09\/11\/kras-g12c-inhibition-induced-enrichment-of-mhc-ihigh-immune-active-tumor-cells-directs-immune-effector-tme-development-to-augment-therapeutic-efficacy\/\" aria-label=\"Read more about KRAS-G12C inhibition-induced enrichment of MHC-Ihigh immune-active tumor cells directs immune-effector TME development to augment therapeutic efficacy\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-76293","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\/76293","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=76293"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/76293\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=76293"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=76293"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=76293"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}