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Title: Expression data for CD8 TILs subpopulations sorted by Tim3 and PD1      
keywords:
Transcriptome or Gene expression
ID:
PRJNA340094
description:
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. Overall design: Samples were generated of naive (CD62LhiCD44low) and effector/memory (CD62LlowCD44hi) CD8+ cells from non tumor-bearing Balb/c mice, CD8+Tim3-PD1- (DN) TILs, CD8+Tim3-PD1+(SP), and CD8+Tim3+PD1+ (DP) TILs. Batch indicated in sample name (2157, 1962, 1635, 1655 and 1716).
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA340094
authentication:
none
authorization:
none
ID:
pmid:27610572
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • U24 CA180922/CA/NCI NIH HHS/United States

  • R01 NS045937/NS/NINDS NIH HHS/United States

  • P30 CA014051/CA/NCI NIH HHS/United States

  • R01 CA187975/CA/NCI NIH HHS/United States

  • Howard Hughes Medical Institute/United States

  • P01 AI045757/AI/NIAID NIH HHS/United States

  • P01 AI073748/AI/NIAID NIH HHS/United States

  • RM1 HG006193/HG/NHGRI NIH HHS/United States

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