|
| Status |
Public on Feb 28, 2017 |
| Title |
Exhaustion-associated regulatory regions in CD8+ tumor-infiltrating T cells (ATAC-seq for in-vivo experiments) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
T cell exhaustion is a progressive loss of effector function and memory potential due to persistent antigen exposure, which occurs in chronic viral infections and cancer. Here we investigate the relation between gene expression and chromatin accessibility in CD8+ tumor-infiltrating lymphocytes (TIL) that recognize a model tumor antigen and have features of both activation and functional exhaustion. By filtering out accessible regions observed in bystander, non-exhausted, TIL and in acutely restimulated CD8+ T cells, we define a pattern of chromatin accessibility specific for T cell exhaustion, characterized by enrichment for consensus binding motifs for Nr4a and NFAT transcription factors. Anti-PD-L1 treatment of tumor-bearing mice results in cessation of tumor growth and partial rescue of cytokine production by the dysfunctional TIL, with only limited changes in gene expression and chromatin accessibility. Our studies provide a valuable resource for the molecular understanding of T cell exhaustion in cancer and other inflammatory settings.
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| |
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| Overall design |
Chromatin accessibility by ATAC-seq in CD8+ tumor-infiltrating lymphocytes
|
| |
|
| Contributor(s) |
Spreafico R |
| Citation(s) |
28283662 |
| |
| Submission date |
Dec 29, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Roberto Spreafico |
| Organization name |
University of Califonia Los Angeles
|
| Department |
Institute for Quantitative and Computational Biosciences
|
| Street address |
UCLA
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE93014 |
Exhaustion-associated regulatory regions in CD8+ tumor-infiltrating T cells |
|
| Relations |
| BioProject |
PRJNA359374 |
| SRA |
SRP095820 |
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