{"id":34239,"date":"2025-06-05T18:49:31","date_gmt":"2025-06-05T16:49:31","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/06\/05\/sustained-macrophage-reprogramming-is-required-for-cd8-t-cell-dependent-long-term-tumor-eradication\/"},"modified":"2025-06-05T18:49:31","modified_gmt":"2025-06-05T16:49:31","slug":"sustained-macrophage-reprogramming-is-required-for-cd8-t-cell-dependent-long-term-tumor-eradication","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/06\/05\/sustained-macrophage-reprogramming-is-required-for-cd8-t-cell-dependent-long-term-tumor-eradication\/","title":{"rendered":"Sustained macrophage reprogramming is required for CD8+ T cell-dependent long-term tumor eradication"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Jun 5. doi: 10.1158\/2326-6066.CIR-24-0797. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Tumor-associated macrophages (TAMs) exhibit a dual role in tumor progression and antitumor immunity. However, understanding the functional states and molecular mechanisms of antitumor TAMs remains a challenge. Herein, we show that intratumoral administration of a combination of agonists against TLR3 and CD40 (hereafter termed myeloid cell treatment, MCT) reprogrammed TAMs in situ to adopt a protective antitumor phenotype in an orthotopic mouse breast cancer model, and that this led to tumor regression. Single-cell RNA sequencing of TAMs from different tumor stages and post-MCT revealed a transient antitumor TAM phenotype, present at 12h post-MCT, characterized by markers such as iNOS and CD38, which was replaced by TAMs co-expressing tumor-limiting and promoting features by 72h post-MCT. Maintenance of antitumor TAMs required repeated MCT administration, and this promoted the activation of CD8+ T cells and long-term tumor eradication. Mechanistically, ROS and TNF-\u03b1 were pivotal in TAM-mediated tumor control. Our findings uncover the vulnerability of transient TAM reprogramming and show that it can be overcome by repeated MCT administrations to sustain efficient antitumor immune responses.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40471151\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250605124929&amp;v=2.18.0.post9+e462414\">40471151<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-0797\">10.1158\/2326-6066.CIR-24-0797<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Jun 5. doi: 10.1158\/2326-6066.CIR-24-0797. Online ahead of print. ABSTRACT Tumor-associated macrophages (TAMs) exhibit a dual role in tumor progression and antitumor immunity. However, understanding the functional states and molecular mechanisms of antitumor TAMs remains a challenge. Herein, we show that intratumoral administration of a combination of agonists against TLR3 and CD40 &#8230; <a title=\"Sustained macrophage reprogramming is required for CD8+ T cell-dependent long-term tumor eradication\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/06\/05\/sustained-macrophage-reprogramming-is-required-for-cd8-t-cell-dependent-long-term-tumor-eradication\/\" aria-label=\"Read more about Sustained macrophage reprogramming is required for CD8+ T cell-dependent long-term tumor eradication\">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-34239","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\/34239","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=34239"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/34239\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=34239"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=34239"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=34239"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}