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Series GSE128591 Query DataSets for GSE128591
Status Public on May 14, 2019
Title Acetate promotes T cell effector function during glucose restriction [RNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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 rescued effector function in glucose-restricted CD8+ T cells. Mechanistically, acetate promoted histone acetylation and chromatin accessibility, and enhanced IFN-γ gene transcription and cytokine production in an acetyl-CoA synthetase (ACSS)-dependent manner. Ex vivo acetate treatment increased IFN-γ production by exhausted T cells, while reducing ACSS expression in T cells impaired 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.
Overall design RNA-seq was performed on acute (24h) or prolonged (120h) glucose restriction (1mM) CD8+ T cells exposed or not to 5mM Acetate, then restimulated for 4h with PMA/Ionomycin.
Contributor(s) Qiu J, Villa M, Sanin DE, Buck MD, O’Sullivan D, Ching R, Matsushita M, Grzes KM, Winkler F, Chang C, Curtis JD, Kyle RL, van Teijlingen Bakker N, Corrado M, Hässler F, Alfei F, Edwards-Hicks J, Maggi LB Jr, Zehn D, Egawa T, Bengsch B, Klein Geltink RI, Jenuwein T, Pearce EJ, Pearce EL
Citation(s) 31091446
Submission date Mar 20, 2019
Last update date Feb 17, 2020
Contact name Immunometabolism Department
Organization name Johns Hopkins University
Department Immunometabolism
Street address 1650 Orleans Street
City Baltimore
State/province Maryland
ZIP/Postal code 21287
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (10)
GSM3680714 d5_1mM_1
GSM3680715 d5_1mM_2
GSM3680716 d5_Acetate_1
This SubSeries is part of SuperSeries:
GSE128594 Acetate promotes T cell effector function during glucose restriction
BioProject PRJNA528257
SRA SRP188953

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Supplementary file Size Download File type/resource
GSE128591_RAW.tar 2.1 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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