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We aimed to explore the immune\u2010related tumor\u2010promoting effects of TSP1 and decipher its underlying mechanism. First, we identified that TSP1 regulated programmed death\u2010ligand 1 (PD\u2010L1) expression, which was related to the CD8<jats:sup>+<\/jats:sup> T cells anergy in osteosarcoma cells. The exact role of PD\u2010L1 in the immunosuppressive effect of TSP1 was then further confirmed by the addition of the PD\u2010L1 neutralizing Ab. With the addition of PD\u2010L1 neutralizing Abs during cocultivation, the inhibition of CD8<jats:sup>+<\/jats:sup> T cells was abolished to a certain extent. Further mechanistic investigations showed that TSP1\u2010induced PD\u2010L1 upregulation was achieved by activation of the signal transducer and activator of transcription 3 (STAT3) pathway. In vivo experiments also indicated that TSP1 overexpression could promote the growth of primary lesions, whereas TSP1 knockdown effectively inhibits the growth of the primary lesion as well as lung metastasis by restoring the antitumor immunity. Thrombospondin\u20101 knockdown combined with PD\u2010L1 neutralizing Ab achieved a more pronounced antitumor effect. Taken together, our study showed that TSP1 upregulates PD\u2010L1 by activating the STAT3 pathway and, therefore, impairs the antitumor immunity against osteosarcoma.<\/jats:p>","DOI":"10.1111\/cas.15237","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T05:52:55Z","timestamp":1639979575000},"page":"432-445","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Thrombospondin\u20101 induced programmed death\u2010ligand 1\u2010mediated immunosuppression by activating the STAT3 pathway in osteosarcoma"],"prefix":"10.1111","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9864-5952","authenticated-orcid":false,"given":"Zhuochao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Orthopedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopedics Ruijin Hospital Shanghai Jiao 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