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Programmed cell death protein 1 (PD\u20101) is known to be expressed on Tregs and plays crucial roles in suppressing tumor immunity. However, the immune checkpoint inhibitor, anti\u2010PD\u20101 antibody, is known to promote the proliferation of the Treg population in tumor\u2010infiltrating lymphocytes, thereby restricting the efficacy of cancer immunotherapy. In this study, we focused on the curcumin analog GO\u2010Y030, an antitumor chemical. GO\u2010Y030 inhibited the immune\u2010suppressive ability of Tregs via metabolic changes in vitro, even in the presence of immune checkpoint inhibitors. Mechanistically, GO\u2010Y030 inhibited the mTOR\u2010S6 axis in Tregs, which plays a pivotal role in their immune\u2010suppressive ability. GO\u2010Y030 also controlled the metabolism in cultured CD4<jats:sup>+<\/jats:sup> T cells in the presence of TGF\u2010\u03b2\u00a0+\u00a0IL\u20106; however, it did not prevent Th17 differentiation. Notably, GO\u2010Y030 significantly inhibited IL\u201010 production from Th17 cells. In the tumor microenvironment, L\u2010lactate produced by tumors is known to support the suppressive ability of Tregs, and GO\u2010Y030 treatment inhibited L\u2010lactate production via metabolic changes. In addition, experiments in the B16\u2010F10 melanoma mouse model revealed that GO\u2010Y030 helped inhibit the anti\u2010PD\u20101 immune checkpoint and reduce the Treg population in tumor\u2010infiltrating lymphocytes. Thus, GO\u2010Y030 controls the metabolism of both Tregs and tumors and could serve as a booster for anti\u2010immune checkpoint inhibitors.<\/jats:p>","DOI":"10.1111\/cas.15136","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T17:22:31Z","timestamp":1631812951000},"page":"4844-4852","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Curcumin analog GO\u2010Y030 boosts the efficacy of anti\u2010PD\u20101 cancer immunotherapy"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0820-3219","authenticated-orcid":false,"given":"Takashi","family":"MaruYama","sequence":"first","affiliation":[{"name":"Mucosal Immunology Section NIDCR, National Institute of Health Bethesda MD USA"},{"name":"Department of Immunology Graduate School of Medicine Akita University Akita 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