Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Qiu, J; Villa, M; Sanin, DE; Buck, MD; O'Sullivan, D; Ching, R; Matsushita, M; Grzes, KM; Winkler, F; Chang, CH; Curtis, JD; Kyle, RL; Bakker, NV; Corrado, M; Haessler, F; Alfei, F; Edwards-Hicks, J; Maggi, LB; Zehn, D; Egawa, T; Bengsch, B; Geltink, RIK; Jenuwein, T; Pearce, EJ; Pearce, EL.
Acetate Promotes T Cell Effector Function during Glucose Restriction
CELL REP. 2019; 27(7): 2063-+.
Doi: 10.1016/j.celrep.2019.04.022
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
- Villa Matteo
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- 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.