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Metabolism

Tumour-derived d-2HG blocks T cell cytotoxicity

Nature Reviews Cancer volume 22, page 657 (2022)Cite this article

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d-2-hydroxyglutarate (d-2HG) is a metabolite produced by tumours with gain-of-function mutations in the genes encoding isocitrate dehydrogenase (IDH). d-2HG accumulates at high concentrations in the tumour microenvironment (TME), and previous in vitro studies have shown that it causes epigenetic changes that lead to oncogenic transformation; however, the effect of d-2HG on cells of the TME — such as cytotoxic (CD8+) T cells — is unclear. In a study published in Science, Notarangelo et al. demonstrate that d-2HG inhibits the anti-tumour activity of CD8+ T cells in the TME by inhibiting their ability to perform glycolysis.

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  1. Nature Reviews Cancer http://www.nature.com/nrc/

    Joseph Willson

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  1. Joseph Willson
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Correspondence to Joseph Willson.

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Willson, J. Tumour-derived d-2HG blocks T cell cytotoxicity. Nat Rev Cancer 22, 657 (2022). https://doi.org/10.1038/s41568-022-00534-6

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  • DOI: https://doi.org/10.1038/s41568-022-00534-6

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