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Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate.

Nat. Med.. 2018;

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Peptide Synthesis	Murine MOG p35-55 peptide MEVGWYRSPFSRVVHLYRNGK was synthesized by Genscript.	Get A Quote

摘要

The oncometabolite (R)-2-hydroxyglutarate (R-2-HG) produced by isocitrate dehydrogenase (IDH) mutations promotes gliomagenesis via DNA and histone methylation. Here， we identify an additional activity of R-2-HG: tumor cell-derived R-2-HG is taken up by T cells where it induces a perturbation of nuclear factor of activated T cells transcriptional activity and polyamine biosynthesis， resulting in suppression of T cell activity. IDH1-mutant gliomas display reduced T cell abundance and altered calcium signaling. Antitumor immunity to experimental syngeneic IDH1-mutant tumors induced by IDH1-specific vaccine or checkpoint inhibition is improved by inhibition of the neomorphic enzymatic function of mutant IDH1. T... More