{"id":35367,"date":"2025-06-13T18:48:35","date_gmt":"2025-06-13T16:48:35","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/06\/13\/tumor-cell-intrinsic-decr2-regulates-ferroptosis-and-immunotherapy-efficacy\/"},"modified":"2025-06-13T18:48:35","modified_gmt":"2025-06-13T16:48:35","slug":"tumor-cell-intrinsic-decr2-regulates-ferroptosis-and-immunotherapy-efficacy","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/06\/13\/tumor-cell-intrinsic-decr2-regulates-ferroptosis-and-immunotherapy-efficacy\/","title":{"rendered":"Tumor cell-intrinsic Decr2 regulates ferroptosis and immunotherapy efficacy"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Jun 13. doi: 10.1158\/2326-6066.CIR-24-0519. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Immune checkpoint blockade therapies have transformed the landscape of cancer care, but durable clinical responses are achieved in only a subset of patients. To identify genes that can contribute to immunotherapy resistance, a genome-wide CRISPR screen was performed. Selection for mutants resistant to T cell-mediated killing identified the gene encoding Decr2, a peroxisomal 2,4-dienoyl-CoA reductase. We show that Decr2 in tumor cells participates in CD8+ T cell-mediated tumor cell killing and that Decr2 knockdown reduces the efficacy of anti-PD-L1 therapy in vivo. Knocking down Decr2 expression resulted in diminished ferroptosis which was associated with reduced induction of polyunsaturated ether phospholipids (PUFA-ePLs). Analysis of tumor RNAseq data from human melanoma patients revealed that up-regulation of Decr2 was associated with anti-PD-1 efficacy, and patients with Decr2 gene deletions showed worse clinical outcomes. Our results identify Decr2 as a regulator of immune-mediated tumor cell killing, with implications for improving immunotherapy efficacy.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40512146\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250613124833&amp;v=2.18.0.post9+e462414\">40512146<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-0519\">10.1158\/2326-6066.CIR-24-0519<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Jun 13. doi: 10.1158\/2326-6066.CIR-24-0519. Online ahead of print. ABSTRACT Immune checkpoint blockade therapies have transformed the landscape of cancer care, but durable clinical responses are achieved in only a subset of patients. To identify genes that can contribute to immunotherapy resistance, a genome-wide CRISPR screen was performed. Selection for mutants resistant &#8230; <a title=\"Tumor cell-intrinsic Decr2 regulates ferroptosis and immunotherapy efficacy\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/06\/13\/tumor-cell-intrinsic-decr2-regulates-ferroptosis-and-immunotherapy-efficacy\/\" aria-label=\"Read more about Tumor cell-intrinsic Decr2 regulates ferroptosis and immunotherapy efficacy\">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-35367","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\/35367","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=35367"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/35367\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=35367"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=35367"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=35367"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}