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RNA sequencing analysis of human ICC samples revealed that, among m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010related regulators, YTHDF1 exhibited the most significant negative correlation with immune score. In multiple ICC mouse models, Ythdf1 overexpression enhanced the recruitment of myeloid\u2010derived suppressor cells (MDSCs) and suppressed cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses, promoting ICC progression. Immunostaining of human ICC tissue microarray verified that high YTHDF1 protein expression was significantly associated with increased accumulation of MDSCs and decreased infiltration of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Mechanistically, YTHDF1 bound to the m\n                    <jats:sup>6<\/jats:sup>\n                    A site of\n                    <jats:italic>FOSL2<\/jats:italic>\n                    mRNA and promoted the translation of FOSL2, a transcription factor driving cytokine CXCL6 expression. Consequently, elevated CXCL6 recruited and activated MDSCs by binding to its receptor CXCR2, leading to the dysfunction of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in ICCs. In addition, targeting YTHDF1 alongside blockade of its downstream chemokine pathway enhanced the efficacy of anti\u2010PD\u2010L1 treatment in preclinical ICC mouse models, serving a promising strategy for improving immunotherapy efficacy in ICC.\n                  <\/jats:p>","DOI":"10.1002\/advs.202520403","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T10:09:30Z","timestamp":1776074970000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting m\n                    <sup>6<\/sup>\n                    A Reader YTHDF1 Enhances Antitumor Immunity and Potentiates Anti\u2010PD\u2010L1 Efficacy in Intrahepatic Cholangiocarcinoma"],"prefix":"10.1002","volume":"13","author":[{"given":"Li","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Oncology the First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong Province 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