IDH-Mutant Brain Tumors Hit the Achilles' Heel of Macrophages with R-2-Hydroxyglutarate

Trends Cancer. 2021 Aug;7(8):666-667. doi: 10.1016/j.trecan.2021.06.003. Epub 2021 Jun 26.

Abstract

Isocitrate dehydrogenase (IDH) mutations produce high levels of the 'oncometabolite' R-2-hydroxyglutarate (R-2-HG) and play a key role in the initiation and progression of glioma tumors in the brain. A recent study in Nature Cancer by Friedrich et al. describes how IDH-mutant-derived R-2-HG elicits an immunosuppressive phenotype in glioma-associated macrophages. As such, the authors uncovered a new vulnerability that can be exploited for therapy.

Keywords: R-2-hydroxyglutarate (R-2-HG); immunometabolism; immunosuppression; immunotherapy; isocitrate dehydrogenase (IDH)-mutant gliomas; tumor-associated macrophages.

MeSH terms

  • Brain Neoplasms*
  • Glutarates
  • Humans
  • Isocitrate Dehydrogenase*
  • Macrophages

Substances

  • Glutarates
  • alpha-hydroxyglutarate
  • Isocitrate Dehydrogenase