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Series GSE144583 Query DataSets for GSE144583
Status Public on Sep 01, 2020
Title Disturbed mitochondrial dynamics in CD8+ TIL reinforce epigenetic programming linked with T cell exhaustion
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary The metabolic challenges present in tumors attenuate the metabolic fitness and anti-tumor activity of tumor-infiltrating T lymphocytes (TILs). However, it remains unclear whether persistent metabolic insufficiency can imprint permanent T cell dysfunction. We found that TILs accumulating depolarized mitochondria as a result of declined mitophagy activity display functional, transcriptomic and epigenetic characteristics of terminally exhausted T cells. Mechanistically, declined mitochondrial fitness in TILs is induced by the coordination of T cell receptor stimulation, microenvironmental stressors and PD-1 signal. Forcing the accumulation of depolarized mitochondria with pharmacological interventions induces epigenetic reprogramming for terminal exhaustion, indicating that mitochondrial deregulation is indeed a cause – rather than a consequence – of T cell exhaustion. Furthermore, supplementation with nicotinamide riboside enhances T cell mitochondrial fitness and improved responsiveness to anti-PD-1 treatment. Together, our results reveal new insights on how mitochondrial dynamics and quality orchestrate T cell anti-tumor responses and commitment to the exhaustion program.
Overall design Examination of DNA methylation in in vivo-generated T cells.
Contributor(s) Yu YR, Imrichova H, Wang H, Ho PC
Citation(s) 33020660
Submission date Jan 30, 2020
Last update date Oct 06, 2020
Contact name Hana Imrichova
Organization name CeMM, Vienna
Street address Lazarettgasse 14, AKH BT 25.3
City Vienna
ZIP/Postal code 1090
Country Austria
Platforms (2)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (6)
GSM4291231 WGBS_Tumor_Hi_1
GSM4291232 WGBS_Tumor_Hi_2
GSM4291233 WGBS_Tumor_Hi_3
This SubSeries is part of SuperSeries:
GSE144584 Disturbed mitochondrial dynamics in CD8+ TIL reinforce epigenetic programming linked with T cell exhaustion
BioProject PRJNA604075
SRA SRP246238

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Supplementary file Size Download File type/resource
GSE144583_RAW.tar 960.0 Kb (http)(custom) TAR (of BED)
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Raw data are available in SRA
Processed data provided as supplementary file

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