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  Acetate Promotes T Cell Effector Function during Glucose Restriction

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

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-1E6B-3 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-1E6C-2
Genre: Journal Article

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 Creators:
Qui, Jing1, Author
Mateo, Villa1, Author              
Sanin, David E.1, Author
Buck, Michael D.1, Author
O'Sullivan, David1, Author              
Ching, Reagen1, Author              
Matsushita, Mai1, Author              
Grzes, Katarzyna1, Author              
Winkler, Frances2, Author
Chang, Chih-Hao2, Author
Curtis, Jonathen1, Author
Kyle, Ryan1, Author
B, Nikki Van Teijlingen1, Author
Corrado, Mauro1, Author
Haessler, Fabian1, Author
Alfei, Francesca1, Author
Edwards-Hicks, Joy1, Author
Maggi Jr., Leonard B.2, Author
Zehn, Dietmar2, Author
Egawa, Takeshi2, Author
Bengsch, Bertram2, AuthorKlein-Geltink, Ramon1, Author              Jenuwein, Thomas1, Author              Pearce, Edward J.1, Author              Pearce, Erika L.1, Author               more..
Affiliations:
1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              
2External Organizations, ou_persistent22              

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Free keywords: T cell exhaustion, T cell hyporesponsiveness, T cells, acetate, acetyl-CoA synthetase, chromatin remodeling, effector functions, tumor immunity, tumor-infiltrating lymphocytes
 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.

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Language(s): eng - English
 Dates: 2019
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.celrep.2019.04.022
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Title: Cell Reports
Source Genre: Journal
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Publ. Info: Maryland Heights, MO : Cell Press
Pages: - Volume / Issue: 27 Sequence Number: - Start / End Page: 2063 - 2074 Identifier: ISSN: 2211-1247
CoNE: https://pure.mpg.de/cone/journals/resource/2211-1247