Cancer Cell：山东大学徐云飞/张宗利/荆卫强/潘畅团队揭示胆管癌免疫治疗新靶点

Core Viewpoint - The study reveals that bile acids activate cancer-associated fibroblasts (CAFs) in cholangiocarcinoma, leading to an immunosuppressive microenvironment, which provides potential targets for immunotherapy [4][10]. Group 1: Research Findings - Bile acids specifically activate GPBAR1 on CAFs, leading to increased expression of CXCL10, which enhances epithelial-mesenchymal transition (EMT) and metastasis in cholangiocarcinoma [6]. - The study found that high levels of bile acids and GPBAR1 expression correlate with poor prognosis and inadequate response to immunotherapy in cholangiocarcinoma patients [7]. - Targeting the GPBAR1-CXCL10 signaling axis can enhance the efficacy of anti-PD-1 monoclonal antibodies in various preclinical models of cholangiocarcinoma [6][8]. Group 2: Implications for Immunotherapy - The bile acid-GPBAR1 signaling axis reprograms CAFs to establish an immunosuppressive microenvironment in cholangiocarcinoma [8]. - CXCL10 produced by CAFs recruits neutrophils and maintains their immature phenotype, contributing to the immunosuppressive tumor microenvironment [8]. - The activation of CXCR3 by the GPBAR1-CXCL10 signaling axis promotes EMT in cholangiocarcinoma cells [8].