{"id":21180,"date":"2025-01-02T19:46:01","date_gmt":"2025-01-02T18:46:01","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/01\/02\/lung-cancer-intrinsic-sox2-expression-mediates-resistance-to-checkpoint-blockade-therapy-by-inducing-treg-cell-dependent-cd8-t-cell-exclusion\/"},"modified":"2025-01-02T19:46:01","modified_gmt":"2025-01-02T18:46:01","slug":"lung-cancer-intrinsic-sox2-expression-mediates-resistance-to-checkpoint-blockade-therapy-by-inducing-treg-cell-dependent-cd8-t-cell-exclusion","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/01\/02\/lung-cancer-intrinsic-sox2-expression-mediates-resistance-to-checkpoint-blockade-therapy-by-inducing-treg-cell-dependent-cd8-t-cell-exclusion\/","title":{"rendered":"Lung cancer-intrinsic SOX2 expression mediates resistance to checkpoint blockade therapy by inducing Treg cell-dependent CD8+ T-cell exclusion"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Jan 2. doi: 10.1158\/2326-6066.CIR-24-0184. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Tumor cell-intrinsic signaling pathways can drastically affect the tumor immune microenvironment, promoting tumor progression and resistance to immunotherapy by excluding immune-cell populations from the tumor. Several tumor cell-intrinsic pathways have been reported to modulate myeloid-cell and T-cell infiltration creating &#8220;cold&#8221; tumors. However, clinical evidence suggests that excluding cytotoxic T cells from the tumor core also mediates immune evasion. Here, we find that tumor cell-intrinsic SOX2 signaling in non-small cell lung cancer induces the exclusion of cytotoxic T cells from the tumor core and promotes resistance to checkpoint blockade therapy. Mechanistically, tumor cell-intrinsic SOX2 expression upregulates CCL2 in tumor cells, resulting in increased recruitment of regulatory T cells. CD8+ T-cell exclusion depended on regulatory T cell-mediated suppression of tumor vasculature. Depleting tumor-infiltrating regulatory T cells via Glucocorticoid-Induced TNFR-Related protein (GITR) restored CD8+ T-cell infiltration and, when combined with checkpoint blockade therapy, reduced tumor growth. These results show that tumor cell-intrinsic SOX2 expression in lung cancer serves as a mechanism of immunotherapy resistance and provide evidence to support future studies investigating whether NSCLC patients with SOX2-dependent CD8+ T-cell exclusion would benefit from the depletion of GITR+ Tregs.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39745382\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250102134600&amp;v=2.18.0.post9+e462414\">39745382<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-0184\">10.1158\/2326-6066.CIR-24-0184<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Jan 2. doi: 10.1158\/2326-6066.CIR-24-0184. Online ahead of print. ABSTRACT Tumor cell-intrinsic signaling pathways can drastically affect the tumor immune microenvironment, promoting tumor progression and resistance to immunotherapy by excluding immune-cell populations from the tumor. Several tumor cell-intrinsic pathways have been reported to modulate myeloid-cell and T-cell infiltration creating &#8220;cold&#8221; tumors. However, &#8230; <a title=\"Lung cancer-intrinsic SOX2 expression mediates resistance to checkpoint blockade therapy by inducing Treg cell-dependent CD8+ T-cell exclusion\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/01\/02\/lung-cancer-intrinsic-sox2-expression-mediates-resistance-to-checkpoint-blockade-therapy-by-inducing-treg-cell-dependent-cd8-t-cell-exclusion\/\" aria-label=\"Read more about Lung cancer-intrinsic SOX2 expression mediates resistance to checkpoint blockade therapy by inducing Treg cell-dependent CD8+ T-cell exclusion\">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-21180","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\/21180","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=21180"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/21180\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=21180"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=21180"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=21180"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}