{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T05:24:28Z","timestamp":1773465868313,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Currently, creating more effector T cells and augmenting their functions is a focal point in pancreatic ductal adenocarcinoma (PDAC) treatment research. T cell immunoglobulin domain and mucin domain molecule 4 (TIM\u20104), known for promoting cancer progression in various malignancies, is implicated in the suppressive immune microenvironment of tumors. Analyzing of the role of TIM\u20104 in the immune regulation of PDAC can offer novel insights for immune therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the TIM\u20104 expression in tumor specimens from PDAC patients. Meanwhile, multiple fluorescent immunohistochemical staining was used to study the distribution characteristics of TIM\u20104, and through tissue microarrays, we explored its correlation with patient prognosis. The influence of TIM\u20104 overexpression on cell function was analyzed using RNA\u2010seq. Flow cytometry and ELISA were used for verification. Finally, the relationship between TIM\u20104 and T lymphocytes was analyzed by tissue microarray, and the impacts of TIM\u20104 on T cell subsets were observed by cell coculture technology and a mouse pancreatic cancer in\u00a0situ model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In PDAC, TIM\u20104 is mainly expressed in tumor cells and negatively correlated with patient prognosis. TIM\u20104 influences the differentiation of Treg by inhibiting IL\u20106 secretion in pancreatic cancer cells and facilitates the proliferation of pancreatic cancer in mice. Additionally, the mechanism may be through the CD8<jats:sup>+<\/jats:sup> effector T cells (CD8<jats:sup>+<\/jats:sup>Tc).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>TIM\u20104 has the potential to be an immunotherapeutic target or to improve the efficacy of chemotherapy for PDAC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70110","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T11:46:18Z","timestamp":1725536778000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>TIM<\/scp>\u20104 increases the proportion of <scp>CD4<\/scp><sup>+<\/sup><scp>CD25<\/scp><sup>+<\/sup><scp>FOXP3<\/scp><sup>+<\/sup> regulatory T cells in the pancreatic ductal adenocarcinoma microenvironment by inhibiting <scp>IL<\/scp>\u20106 secretion"],"prefix":"10.1002","volume":"13","author":[{"given":"Ziyao","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Pancreatic Surgery, Department of General Surgery West China Hospital, Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zerong","family":"Xie","sequence":"additional","affiliation":[{"name":"Division of Pancreatic Surgery, Department of General Surgery West China Hospital, Sichuan University  Chengdu China"},{"name":"Department of General Surgery West China Tianfu Hospital, Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Mou","sequence":"additional","affiliation":[{"name":"Division of Pancreatic Surgery, Department of General Surgery West China Hospital, Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruiman","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology West China School of Basic Medical Sciences &amp; Forensic Medicine, Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology The First People's Hospital of Chengdu  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7135-2244","authenticated-orcid":false,"given":"Nengwen","family":"Ke","sequence":"additional","affiliation":[{"name":"Division of Pancreatic Surgery, Department of General Surgery West China Hospital, Sichuan University  Chengdu 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