Acetate Promotes T Cell Effector Function during Glucose Restriction

Jing Qiu

doi:10.1016/j.celrep.2019.04.022

Acetate Promotes T Cell Effector Function during Glucose Restriction

2019-05-01

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Nikki van Teijlingen Bakker

Ramon I. Klein Geltink

DOI：10.1016/j.celrep.2019.04.022

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Competition for nutrients like glucose can metabolically restrict T cells and contribute to their hypores-ponsiveness 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-gamma gene transcription and cytokine production in an acetyl-CoA synthetase (ACSS)-dependent manner. Ex vivo acetate treatment increases IFN-gamma production by exhausted T cells, whereas reducing ACSS expression in T cells impairs IFN-gamma production by tumor-infiltrating lymphocytes and tumor clearance. Thus, hypores-ponsive 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.

Keywords:

CHAIN FATTY-ACIDS

HISTONE ACETYLATION

GENE-REGULATION

METABOLISM

ACTIVATION

TUMOR

PD-1

GLYCOLYSIS

EXPRESSION

DRIVER

Acetate Promotes T Cell Effector Function during Glucose Restriction

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