Potent immunosuppressive effects of the oncometabolite R-2-hydroxyglutarate. Editorial Article uri icon

Overview

abstract

  • Somatic gain-of-function mutations in isocitrate dehydrogenase (NADP(+)) 1, cytosolic (IDH1) or isocitrate dehydrogenase (NADP(+)) 2, mitochondrial (IDH2) are bona fide oncogenic drivers of acute myeloid leukemia and glioma because the neomorphic enzymes catalyze the synthesis of R-2-hydroxylutarate (R-2-HG), an oncometabolite with robust epigenetic effects. Recent data indicate that R-2-HG released by malignant cells can accumulate in the extracellular space and be taken up by T lymphocytes, ultimately compromising their capacity to mediate anticancer immune responses. Thus, R-2-HG drives oncogenesis and tumor progression not only as a cancer cell-autonomous epigenetic modifier, but also as an immunosuppressive metabolite. Chemical inhibitors of mutant IDH1 and IDH2, which currently are under clinical evaluation, may therefore mediate dual anticancer effects by targeting cancer cells and, at the same time, relieving R-2-HG-mediated immunosuppression.

publication date

  • October 16, 2018

Identity

PubMed Central ID

  • PMC6279319

Scopus Document Identifier

  • 85055190649

Digital Object Identifier (DOI)

  • 10.1080/2162402X.2018.1528815

PubMed ID

  • 30524910

Additional Document Info

volume

  • 7

issue

  • 12