{"id":70757,"date":"2026-07-17T00:54:22","date_gmt":"2026-07-16T22:54:22","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/07\/17\/elevated-chaf1a-suppresses-type-i-interferon-production-and-causes-immunotherapy-resistance-in-esophageal-squamous-cell-carcinoma\/"},"modified":"2026-07-17T00:54:22","modified_gmt":"2026-07-16T22:54:22","slug":"elevated-chaf1a-suppresses-type-i-interferon-production-and-causes-immunotherapy-resistance-in-esophageal-squamous-cell-carcinoma","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/07\/17\/elevated-chaf1a-suppresses-type-i-interferon-production-and-causes-immunotherapy-resistance-in-esophageal-squamous-cell-carcinoma\/","title":{"rendered":"Elevated CHAF1A suppresses type I interferon production and causes immunotherapy resistance in esophageal squamous cell carcinoma"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 Jul 16. doi: 10.1158\/2326-6066.CIR-25-1617. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>In esophageal squamous cell carcinoma (ESCC), chemoradiotherapy potentiates the effects of immune checkpoint inhibitors (ICIs) by activating the tumor-intrinsic innate immune response. However, ESCC cells frequently suppress this activation, which contributes to the high rates of immunotherapy resistance (70-80%) observed clinically. Thus, identifying intracellular suppressors of this innate immune response remains an unmet critical need. Herein, through multi-omic analyses, we identify the chromatin assembly factor CHAF1A as a suppressor of the tumor-intrinsic innate immune response in ESCC. We found that CHAF1A was overexpressed in ESCC and negatively correlated with type I interferon production and CD8+ T-cell infiltration. Mechanistically, CHAF1A maintained heterochromatin silencing mediated by H3K9me3, thereby repressing endogenous retroviruses (ERVs). This suppression prevented the accumulation of double-stranded RNA (dsRNA) and the subsequent activation of the MAVS-IRF3 signaling pathway. Concurrently, CHAF1A preserved genomic stability, limiting the release of double-stranded DNA (dsDNA) and activation of the cGAS-STING pathway. Loss of CHAF1A potentiated the response to immunotherapy through the coordinated activation of these dual pathways. We then performed a small-molecule compound screen and identified a CHAF1A inhibitor, Baimaside, which enhanced the effect of anti-PD-1 therapy to augment antitumor immunity. Collectively, these data indicate that CHAF1A represents a potential therapeutic target for sensitizing ESCC to immunotherapy and provide a potential combination strategy for reversing immunotherapy resistance.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42462139\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260716185421&amp;v=2.20.0\">42462139<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-1617\">10.1158\/2326-6066.CIR-25-1617<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 Jul 16. doi: 10.1158\/2326-6066.CIR-25-1617. Online ahead of print. ABSTRACT In esophageal squamous cell carcinoma (ESCC), chemoradiotherapy potentiates the effects of immune checkpoint inhibitors (ICIs) by activating the tumor-intrinsic innate immune response. However, ESCC cells frequently suppress this activation, which contributes to the high rates of immunotherapy resistance (70-80%) observed clinically. Thus, &#8230; <a title=\"Elevated CHAF1A suppresses type I interferon production and causes immunotherapy resistance in esophageal squamous cell carcinoma\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/07\/17\/elevated-chaf1a-suppresses-type-i-interferon-production-and-causes-immunotherapy-resistance-in-esophageal-squamous-cell-carcinoma\/\" aria-label=\"Read more about Elevated CHAF1A suppresses type I interferon production and causes immunotherapy resistance in esophageal squamous cell carcinoma\">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-70757","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\/70757","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=70757"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/70757\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=70757"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=70757"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=70757"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}