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While surgical resection followed by adjuvant S-1 therapy is the standard curative treatment for BTC, long-term postoperative remission is hardly achieved. Therefore, more effective perioperative strategies are urgently needed. Here, we show that an immune-cold tumor microenvironment (TME) in KRAS-mutated BTC correlated with resistance to postoperative adjuvant S-1 therapy. Surgically resected tumor specimens were collected from 31 BTC patients who received adjuvant S-1 therapy after surgery and were subjected to integrated immunogenomic analysis, including multiplexed immunohistochemistry staining and whole-exome sequencing. The analysis revealed a strong correlation between limited CD8\u207a T cell and antigen-presenting cell (APC) infiltration into the TME and KRAS mutations in BTC. In addition, the distances between tumor cells and APCs, as well as between APCs and CD8\u207a T cells, were significantly greater in the TME of KRAS-mutated BTC than in that of KRAS wild-type BTC. These findings indicate that interactions between effector T cells and APCs were impaired in the TME of KRAS-mutated BTC, thereby disrupting antitumor immune responses. Furthermore, wild-type KRAS and abundant CD8\u207a T cells and APCs correlated with a favorable prognosis following adjuvant S-1 therapy for BTC. Altogether, we propose a novel immunogenomic-based biomarker for optimizing perioperative chemotherapy for BTC.<\/jats:p>","DOI":"10.1093\/intimm\/dxaf065","type":"journal-article","created":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:04:53Z","timestamp":1762002293000},"page":"236-250","source":"Crossref","is-referenced-by-count":3,"title":["<i>KRAS<\/i>\n                    mutations disrupt interactions between CD8+ T cells and antigen-presenting cells in the tumor microenvironment of biliary tract cancer"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1562-3265","authenticated-orcid":false,"given":"Fumihiro","family":"Terasaki","sequence":"first","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine , Nagoya 466-8550 ,","place":["Japan"]},{"name":"Division of Cancer Immunology, Research Institute, National Cancer Center , Tokyo 104-0045 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