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• W4298006543 abstract "Gain-of-function mutations in isocitrate dehydrogenase (IDH) in human cancers result in the production of d-2-hydroxyglutarate (d-2HG), an oncometabolite that promotes tumorigenesis through epigenetic alterations. The cancer cell-intrinsic effects of d-2HG are well understood, but its tumor cell-nonautonomous roles remain poorly explored. We compared the oncometabolite d-2HG with its enantiomer, l-2HG, and found that tumor-derived d-2HG was taken up by CD8+ T cells and altered their metabolism and antitumor functions in an acute and reversible fashion. We identified the glycolytic enzyme lactate dehydrogenase (LDH) as a molecular target of d-2HG. d-2HG and inhibition of LDH drive a metabolic program and immune CD8+ T cell signature marked by decreased cytotoxicity and impaired interferon-γ signaling that was recapitulated in clinical samples from human patients with IDH1 mutant gliomas." @default.
• W4298006543 created "2022-10-01" @default.
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• W4298006543 date "2022-09-30" @default.
• W4298006543 modified "2023-10-14" @default.
• W4298006543 title "Oncometabolite <scp>d</scp> -2HG alters T cell metabolism to impair CD8 ⁺ T cell function" @default.
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• W4298006543 doi "https://doi.org/10.1126/science.abj5104" @default.
• W4298006543 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36173860" @default.
• W4298006543 hasPublicationYear "2022" @default.
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