Document Type
Article
Publication Date
5-14-2019
Keywords
JMG
JAX Source
Cell Rep 2019 May 14; 27(7):2063-74.
Volume
27
Issue
7
First Page
2063
Last Page
2074
ISSN
2211-1247
PMID
31091446
DOI
https://doi.org/10.1016/j.celrep.2019.04.022
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-γ gene transcription and cytokine production in an acetyl-CoA synthetase (ACSS)-dependent manner. Ex vivo acetate treatment increases IFN-γ production by exhausted T cells, whereas reducing ACSS expression in T cells impairs IFN-γ 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.
Recommended Citation
Qiu J,
Villa M,
Sanin D,
Buck M,
O'Sullivan D,
Ching R,
Matsushita M,
Grzes K,
Winkler F,
Chang C,
Curtis J,
Kyle R,
Van Teijlingen Bakker N,
Corrado M,
Haessler F,
Alfei F,
Edwards-Hicks J,
Maggi L,
Zehn D,
Egawa T,
Bengsch B,
Klein Geltink R,
Jenuwein T,
Pearce E,
Pearce E.
Acetate Promotes T Cell Effector Function during Glucose Restriction. Cell Rep 2019 May 14; 27(7):2063-74.
Comments
This article is available under the Creative Commons BY-NC-ND license.