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This study aims to explore the association of FGFR2 status with the prognosis and immune cell infiltration profiles of patients with ICC. A total of 226 ICC tissue samples from patients who received surgery at the Department of Liver Surgery at Zhongshan Hospital, Fudan University, were collected retrospectively and assigned to a primary cohort (n\u2005=\u2005152) and validation cohort (n\u2005=\u200574) group. Fluorescence in situ hybridization was performed to determine FGFR2 status. Multiplex immunofluorescence (mIF) staining and immunohistochemistry were performed to identify immune cells. Thirty-two (14.2%) ICC tissues presented with FGFR2 fusion\/rearrangement. FGFR2 fusion\/rearrangement was associated with low levels of carcinoembryonic antigen (CEA, P\u2005=\u2005.026) and gamma glutamyl transferase (\u03b3-GGT, P\u2005=\u2005.003), low TNM (P\u2005=\u2005.012), CNLC (P\u2005=\u2005.008) staging as well as low tumor cell differentiation (P\u2005=\u2005.016). Multivariate COX regression analyses revealed that FGFR2 fusion\/rearrangement was an independent protective factor for both overall survival (OS) and relapse-free survival in patients with ICC. Furthermore, correlation analysis revealed that an FGFR2 fusion\/rearrangement was associated with low levels of Tregs and N2 neutrophils and high levels of N1 neutrophils infiltrating into tumors but not with CD8+ T-cell or macrophage tumor infiltration. FGFR2 fusion\/rearrangement may exert a profound impact on the prognosis of ICC patients and reprogram the tumor microenvironment to be an immune-activated state. FGFR2 status may be used for ICC prognostic stratification and as an immunotherapeutic target in patients with ICC.<\/jats:p>","DOI":"10.1093\/oncolo\/oyae170","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T02:20:43Z","timestamp":1719195643000},"page":"e1734-e1747","source":"Crossref","is-referenced-by-count":14,"title":["<i>FGFR2<\/i>\n                    fusion\/rearrangement is associated with favorable prognosis and immunoactivation in patients with intrahepatic cholangiocarcinoma"],"prefix":"10.1093","volume":"29","author":[{"given":"Shaoqing","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education , Shanghai, 200032 ,","place":["People\u2019s Republic of China"]},{"name":"Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive 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Ministry of Education , Shanghai, 200032 ,","place":["People\u2019s Republic of China"]},{"name":"Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission , Shanghai, 201199 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education , Shanghai, 200032 ,","place":["People\u2019s Republic of China"]},{"name":"Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission , Shanghai, 201199 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiu","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission , Shanghai, 201199 ,","place":["People\u2019s Republic of China"]},{"name":"Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University , Shanghai, 201199 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education , Shanghai, 200032 ,","place":["People\u2019s Republic of China"]},{"name":"Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission , Shanghai, 201199 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongzhu","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission , Shanghai, 201199 ,","place":["People\u2019s Republic of China"]},{"name":"Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University , Shanghai, 201199 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Sheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission , Shanghai, 201199 ,","place":["People\u2019s Republic of China"]},{"name":"Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan 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