{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:31:28Z","timestamp":1784719888146,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T00:00:00Z","timestamp":1627862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immunotherapy with immune\u2010checkpoint therapy has recently been used to treat oral squamous cell carcinomas (OSCCs). However, improvements in current immunotherapy are expected because response rates are limited. Transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) creates an immunosuppressive tumor microenvironment (TME) by inducing the production of regulatory T\u2010cells (Tregs) and cancer\u2010associated fibroblasts and inhibiting the function of cytotoxic T\u2010lymphocytes (CTLs) and natural killer cells. TGF\u2010\u03b2 may be an important target in the development of novel cancer immunotherapies. In this study, we investigated the suppressive effect of TGF\u2010\u03b2 on CTL function in vitro using OSCC cell lines and their specific CTLs. Moreover, <jats:italic>TGFB1<\/jats:italic> mRNA expression and T\u2010cell infiltration in 25 OSCC tissues were examined by in situ hybridization and multifluorescence immunohistochemistry. We found that TGF\u2010\u03b2 suppressed the function of antigen\u2010specific CTLs in the priming and effector phases in vitro. Additionally, TGF\u2010\u03b2 inhibitor effectively restored the CTL function, and <jats:italic>TGFB1<\/jats:italic> mRNA was primarily expressed in the tumor invasive front. Interestingly, we found a significant negative correlation between <jats:italic>TGFB1<\/jats:italic> mRNA expression and the CD8<jats:sup>+<\/jats:sup> T\u2010cell\/Treg ratio and between <jats:italic>TGFB1<\/jats:italic> mRNA expression and the Ki\u201067 expression in CD8<jats:sup>+<\/jats:sup> T\u2010cells, indicating that TGF\u2010\u03b2 also suppressed the function of CTLs in situ. Our findings suggest that the regulation of TGF\u2010\u03b2 function restores the immunosuppressive TME to active status and is important for developing new immunotherapeutic strategies, such as a combination of immune\u2010checkpoint inhibitors and TGF\u2010\u03b2 inhibitors, for OSCCs.<\/jats:p>","DOI":"10.1111\/cas.15081","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T13:47:45Z","timestamp":1627307265000},"page":"4037-4049","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Improving function of cytotoxic T\u2010lymphocytes by transforming growth factor\u2010\u03b2 inhibitor in oral squamous cell carcinoma"],"prefix":"10.1111","volume":"112","author":[{"given":"Yutaro","family":"Kondo","sequence":"first","affiliation":[{"name":"Department of Maxillofacial Surgery School of Dentistry Aichi Gakuin University Nagoya 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