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Status |
Public on Sep 07, 2016 |
Title |
A distinct gene module uncouples dysfunction from activation in tumor-infiltrating T cells (batch 3) |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8+ tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction, and use CRISPR/Cas9 genome editing to show that it drives a dysfunctional phenotype in CD8+ TILs. Our results open novel avenues for targeting dysfunctional T cell states, while leaving activation programs intact.
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Overall design |
CD8 TILs from WT and MTKO mice were sequenced at single-cell resolution
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Contributor(s) |
Singer M |
Citation(s) |
27610572 |
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Submission date |
Aug 24, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Meromit Singer |
E-mail(s) |
msinger@broadinstitute.org
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Organization name |
Broad Institute of MIT and Harvard
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Street address |
415 main st, ROOM 6031
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City |
CAMBRIDGE |
State/province |
MASSACHUSETTS |
ZIP/Postal code |
02142 |
Country |
USA |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (384)
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This SubSeries is part of SuperSeries: |
GSE86042 |
A distinct gene module uncouples dysfunction from activation in tumor-infiltrating T cells |
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Relations |
BioProject |
PRJNA340023 |
SRA |
SRP082756 |