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Interferon\u2010\u03b3 (IFN\u2010\u03b3)\u2010induced PD\u2010L1 expression might facilitate immunotherapy resistance. Methylseleninic acid (MSeA), a selenium (Se) compound, offered superior cancer chemo\u2010preventive activities and enhanced tumor sensitivity to diverse chemotherapeutic drugs. This study explored the effects of MSeA on the PD\u2010L1\u2010mediated resistance using both in vitro and in vivo models. Results showed that MSeA substantially attenuated cisplatin\u2010induced PD\u2010L1 expression via inhibiting protein kinase B phosphorylation, thereby potentiated cisplatin cytotoxicity in prostate and lung cancer cell models. In lung cancer xenograft model, MSeA significantly suppressed cisplatin\u2010induced PD\u2010L1 expression, consequently enhanced T\u2010cell immunity, ultimately improved the therapeutic efficacy of cisplatin. Moreover, IFN\u2010\u03b3\u2010induced tumor PD\u2010L1 expression was remarkably reduced by MSeA, with correlated reductions in janus kinase 2 and signal transducer and activator of transcription 3 (STAT3) phosphorylation in prostate and lung cancer cell models. Our findings, for the first time, demonstrated that MSeA is a potential agent to overcome PD\u2010L1\u2010mediated chemotherapy and immunotherapy resistance. Such information might have potential clinical implications for prostate and lung cancer treatment.<\/jats:p>","DOI":"10.1002\/mc.23340","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T20:08:42Z","timestamp":1629403722000},"page":"746-757","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Methylseleninic acid overcomes programmed death\u2010ligand 1\u2010mediated resistance of prostate cancer and lung cancer"],"prefix":"10.1002","volume":"60","author":[{"given":"Wenli","family":"Hu","sequence":"first","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yurong","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University Beijing 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