Abstract
The importance of metabolic pathways in regulating immune responses is now well established, and a mapping of the bioenergetic metabolism of different immune cell types is under way. CD8 T cells and natural killer (NK) cells contribute to cancer immunosurveillance through their cytotoxic functions and secretion of cytokines and chemokines, complementing each other in target recognition mechanisms. Several immunotherapies leverage these cell types by either stimulating their activity or redirecting their specificity against tumour cells. However, the anticancer activity of CD8 T cells and NK cells is rapidly diminished in the tumour microenvironment, closely linked to a decline in their metabolic capacities. Various strategies have been developed to restore cancer immunosurveillance, including targeting bioenergetic metabolism or genetic engineering. This Review provides an overview of metabolic dysfunction in CD8 T cells and NK cells within the tumour microenvironment, highlighting current therapies aiming to overcome these issues.
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Acknowledgements
The T.W.–A.M. laboratory at the Centre International de Recherche en Infectiologie is supported by funding from the Agence Nationale de la Recherche, the Institut National du Cancer, the Ligue nationale contre le cancer, the Fondation ARC pour la recherche sur le cancer and institutional grants awarded to the Centre International de Recherche en Infectiologie. The E.V. laboratory at CIML is funded by the European Research Council under the European Union’s Horizon (Treatlivmets, grant agreement no. 101118936), MSDAvenir, Innate Pharma, and institutional grants awarded to the CIML (INSERM, CNRS and Aix-Marseille University). E.V. is “Natural Killer Cells” Chair, Fondation Gustave Roussy.
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Viel, S., Vivier, E., Walzer, T. et al. Targeting metabolic dysfunction of CD8 T cells and natural killer cells in cancer. Nat Rev Drug Discov 24, 190–208 (2025). https://doi.org/10.1038/s41573-024-01098-w
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DOI: https://doi.org/10.1038/s41573-024-01098-w
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