Genomics

Dataset Information

160

Exhaustion-associated regulatory regions in CD8+ tumor-infiltrating T cells (ATAC-seq for in-vitro experiments)


ABSTRACT: 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. Overall design: Chromatin accessibility by ATAC-seq for CD8+ T cells restimulated in vitro

INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)

SUBMITTER: Roberto Spreafico 

PROVIDER: GSE93001 | GEO | 2017-02-28

SECONDARY ACCESSION(S): PRJNA359351

REPOSITORIES: GEO

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Publications

Exhaustion-associated regulatory regions in CD8+ tumor-infiltrating T cells.

Mognol Giuliana P GP   Spreafico Roberto R   Wong Victor V   Scott-Browne James P JP   Togher Susan S   Hoffmann Alexander A   Hogan Patrick G PG   Rao Anjana A   Trifari Sara S  

Proceedings of the National Academy of Sciences of the United States of America 20170310 13


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 (TILs) that recognize a model tumor antigen and have features of both activation and functional exhaustion. By filtering out accessible regions observed in bystander, nonexhausted TILs and in acutely resti  ...[more]

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