{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T20:25:33Z","timestamp":1770495933981,"version":"3.49.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001044"],"award-info":[{"award-number":["82001044"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101015"],"award-info":[{"award-number":["82101015"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Radiation injury is common after radiotherapy for head and neck cancer. Radiotherapy can reshape the immune microenvironment and cause immunosuppression, including dysregulation of immune checkpoints (ICs). However, the relationship between oral ICs expression after radiation and the development of second primary tumors is unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical specimens of second primary oral squamous cell carcinoma after radiotherapy (s\u2010OSCC) and primary OSCC (p\u2010OSCC) were collected. The expression and prognostic value of PD\u20101, VISTA, and TIM\u20103 were analyzed using immunohistochemistry. To further clarify the relationship between radiation and ICs alteration, a rat model was constructed to explore the spatiotemporal changes of ICs in the oral mucosa after radiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In carcinoma tissue, the expression of TIM\u20103 was higher in s\u2010OSCC than in p\u2010OSCC, while the expression of PD\u20101 and VISTA was similar between the groups. In para\u2010carcinoma tissue, the expression of PD\u20101, VISTA, and TIM\u20103 was higher in s\u2010OSCC. High ICs expression was associated with poor survival. In the rat model, ICs were locally upregulated in the irradiated tongue. Moreover, there was a bystander effect, in which the ICs were also upregulated in the unirradiated site.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Radiation may upregulate ICs expression in oral mucosa and contribute to the development of s\u2010OSCC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.14621","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T15:19:52Z","timestamp":1684768792000},"page":"2188-2201","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Radiotherapy upregulated immune checkpoints contribute to the development of second primary <scp>OSCC<\/scp>"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9628-7258","authenticated-orcid":false,"given":"Li","family":"Wang","sequence":"first","affiliation":[{"name":"Hospital of Stomatology Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9690-5514","authenticated-orcid":false,"given":"Siyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Hospital of Stomatology Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8180-5796","authenticated-orcid":false,"given":"Jiayu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hospital of Stomatology Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology Sun Yat\u2010Sen University  Guangzhou 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