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| Status |
Public on May 14, 2019 |
| Title |
Acetate promotes T cell effector function during glucose restriction [ATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| 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.
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| Overall design |
ATAC-seq was performed on acute (24h) or prolonged (120h) glucose restriction (1mM) CD8+ T cells exposed or not to 5mM Acetate.
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| 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 |
| E-mail(s) |
jcurti29@jhmi.edu
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| Organization name |
Johns Hopkins University
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| Department |
Immunometabolism
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| Street address |
1650 Orleans Street
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21287 |
| Country |
USA |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE128594 |
Acetate promotes T cell effector function during glucose restriction |
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| Relations |
| BioProject |
PRJNA528258 |
| SRA |
SRP188952 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE128592_RAW.tar |
178.7 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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