{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T05:10:00Z","timestamp":1761282600927,"version":"build-2065373602"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":295,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82374215"],"award-info":[{"award-number":["82374215"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004921","name":"Shanghai Jiao Tong University","doi-asserted-by":"publisher","award":["YG2023ZD20","YG2022QN086"],"award-info":[{"award-number":["YG2023ZD20","YG2022QN086"]}],"id":[{"id":"10.13039\/501100004921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>Cholangiocarcinoma exhibits a complex tumor microenvironment, yet the cellular interactions governing its progression remain poorly understood. Here, through integrated analysis of two independent single\u2010cell RNA sequencing datasets comprising both complete tissue and immune\u2010focused profiling, we comprehensively mapped the cellular landscape and intercellular communication networks in human cholangiocarcinoma. Our analysis revealed significant remodeling of immune cell compositions and interaction patterns in the tumor microenvironment. Notably, we identified enhanced ICOS signaling between dendritic cells and T cells as a prominent feature of cholangiocarcinoma. Using CellChat analysis, we demonstrated that tumor\u2010associated dendritic cells, particularly plasmacytoid DCs, exhibit stronger ICOS\u2010mediated communication with T cells compared to their counterparts in normal tissues. Functional validation experiments confirmed that tumor\u2010conditioned dendritic cells upregulate ICOSL expression and promote CD8+ T\u2010cell activation through the ICOS\u2013ICOSL axis, as evidenced by increased CD69 and CD25 expression. This activation was specifically abolished by ICOSL blockade, establishing the functional significance of this pathway. Our findings provide novel insights into tumor\u2010immune interactions in cholangiocarcinoma and suggest the ICOS\u2013ICOSL axis as a potential therapeutic target for immunotherapy.<\/jats:p>","DOI":"10.1155\/humu\/9981470","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T05:05:17Z","timestamp":1761282317000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced ICOS Signaling Between Dendritic Cells and T Cells Characterizes the Immune Landscape of Human Cholangiocarcinoma"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7251-0818","authenticated-orcid":false,"given":"Meiying","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8865-0439","authenticated-orcid":false,"given":"Yuou","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4790-7018","authenticated-orcid":false,"given":"Xiaolong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4201-633X","authenticated-orcid":false,"given":"Xinjian","family":"Wan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5052-6428","authenticated-orcid":false,"given":"Zunqiang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31410"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61903-0"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.10.013"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.07.022"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2020.1733528"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32099"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-022-02340-2"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001946"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1037945"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2023.5585"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2019-000544"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00552-7"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-1157"},{"key":"e_1_2_12_14_2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/j.1751-2980.2011.00527.x","article-title":"Immunomodulation 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