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

First Author  Bunse L Year  2018
Journal  Nat Med Volume  24
Issue  8 Pages  1192-1203
PubMed ID  29988124 Mgi Jnum  J:342699
Mgi Id  MGI:6278214 Doi  10.1038/s41591-018-0095-6
Citation  Bunse L, et al. (2018) Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate. Nat Med 24(8):1192-1203
abstractText  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. These data attribute a novel, non-tumor cell-autonomous role to an oncometabolite in shaping the tumor immune microenvironment.
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