@article {694511,
	title = {Oncometabolite D-2HG alters T cell metabolism to impair CD8+ T cell function},
	journal = {Science},
	volume = {377},
	number = {6614},
	year = {2022},
	pages = {1519-1529},
	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{\textendash}intrinsic effects of D-2HG are well understood, but its tumor cell{\textendash}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.},
	url = {https://www.science.org/doi/10.1126/science.abj5104},
	author = {Giulia Notarangelo}
}
