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Tumor\u2010associated macrophages (TAMs) promote malignant progression and immune microenvironment remodeling through direct contact and secreted mediators. Targeting TAMs has emerged as a promising strategy for ICC treatment. Here, we revealed the potential regulatory function of immune responsive gene 1 (IRG1) in macrophage polarization. We found that IRG1 expression remained at a low level in M2 macrophages. IRG1 overexpression can restrain macrophages from polarizing to the M2 type, which results in inhibition of the proliferation, invasion, and migration of ICC, whereas IRG1 knockdown exerts the opposite effects. Mechanistically, IRG1 inhibited the tumor\u2010promoting chemokine CCL18 and thus suppressed ICC progression by regulating STAT3 phosphorylation. The intervention of IRG1 expression in TAMs may serve as a potential therapeutic target for delaying ICC progression.<\/jats:p>","DOI":"10.1111\/cas.16068","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T03:06:30Z","timestamp":1705460790000},"page":"777-790","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<scp>IRG1<\/scp> restrains <scp>M2<\/scp> macrophage polarization and suppresses intrahepatic cholangiocarcinoma progression via the <scp>CCL18<\/scp>\/<scp>STAT3<\/scp> pathway"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3396-5269","authenticated-orcid":false,"given":"Menghua","family":"Zhou","sequence":"first","affiliation":[{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Minimally Invasive Hepatic Surgery The First Affiliated Hospital of Harbin Medical University  Harbin 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