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

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Cell reports. - 27, 7 (2019) , 2063-2074.e5, ISSN: 2211-1247

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2020
• Urheber: 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.

Weitere Informationen

• DOI: 10.1016/j.celrep.2019.04.022
• URN: urn:nbn:de:bsz:25-freidok-1550325
• Rechteinformation: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 14.08.2025, 10:54 MESZ