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Journal Article

Acetate Promotes T cell Effector Function during Glucose Restriction

MPS-Authors

Haessler,  Fabian
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Alfei,  Francesca
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Maggi,  Leonard B. Jr.
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Zehn,  Dietmar
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Egawa,  Takeshi
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Qiu, J., Villa, M., Sanin, D. E., Buck, M. D., O'Sullivan, D., Ching, R., et al. (2019). Acetate Promotes T cell Effector Function during Glucose Restriction. Cell, 27, 2063-2074. doi:10.1016/j.celrep.2019.04.022.


Cite as: http://hdl.handle.net/21.11116/0000-0008-8328-7
Abstract
Competition for nutrients like glucose can metabolically restrict T cells and contribute to their hyporesponsiveness during cancer. Metabolic adaptation to the surrounding microenvironment is therefore key for maintaining appropriate cell function. For instance, cancer cells use acetate as a substrate alternative to glucose to fuel metabolism and growth. Here, we show that acetate rescues effector function in glucose-restricted CD8+ T cells. Mechanistically, acetate promotes histone acetylation and chromatin accessibility and enhances IFN-ɣ gene transcription and cytokine production in an acetyl-CoA synthetase (ACSS)-dependent manner. Ex vivo acetate treatment increases IFN-ɣ production by exhausted T cells, whereas reducing ACSS expression in T cells impairs IFN-ɣ production by tumor-infiltrating lymphocytes and tumor clearance. Thus, hyporesponsive T cells can be epigenetically remodeled and reactivated by acetate, suggesting that pathways regulating the use of substrates alternative to glucose could be therapeutically targeted to promote T cell function during cancer.