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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
E-mail(s) hana.imrichova@gmail.com, himrichova@cemm.oeaw.ac.at
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
Relations
BioProject PRJNA604075
SRA SRP246238

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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

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