Acetate promotes T cell effector function during glucose restriction
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
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Cell reports. - 27, 7 (2019) , 2063-2074.e5, ISSN: 2211-1247
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2020
- Creator
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Qiu, Jing
Villa, Matteo
Sanin, David E.
Buck, Michael D.
O’Sullivan, David
Ching, Reagan
Matsushita, Mai
Grzes, Katarzyna
Winkler, Frances
Chang, Chih-Hao
Curtis, Jonathan D.
Kyle, Ryan L.
Teijlingen Bakker, Nikki Van
Corrado, Mauro
Hässler, Fabian
Alfei, Francesca
Edwards-Hicks, Joy
Maggi, Leonard B.
Zehn, Dietmar
Egawa, Takeshi
Bengsch, Bertram
Klein Geltink, Ramon I.
Jenuwein, Thomas
Pearce, Edward J.
Pearce, Erika L.
- DOI
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10.1016/j.celrep.2019.04.022
- URN
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urn:nbn:de:bsz:25-freidok-1550325
- Rights
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Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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2025-03-25T13:44:07+0100
Data provider
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Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Qiu, Jing
- Villa, Matteo
- Sanin, David E.
- Buck, Michael D.
- O’Sullivan, David
- Ching, Reagan
- Matsushita, Mai
- Grzes, Katarzyna
- Winkler, Frances
- Chang, Chih-Hao
- Curtis, Jonathan D.
- Kyle, Ryan L.
- Teijlingen Bakker, Nikki Van
- Corrado, Mauro
- Hässler, Fabian
- Alfei, Francesca
- Edwards-Hicks, Joy
- Maggi, Leonard B.
- Zehn, Dietmar
- Egawa, Takeshi
- Bengsch, Bertram
- Klein Geltink, Ramon I.
- Jenuwein, Thomas
- Pearce, Edward J.
- Pearce, Erika L.
- Universität
Time of origin
- 2020
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