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Title: A distinct gene module uncouples dysfunction from activation in tumor-infiltrating T cells (batch 2)      
keywords:
Transcriptome or Gene expression
ID:
PRJNA340084
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: CD8 TILs from WT and MTKO mice were sequenced at single-cell resolution
accesstypes:
download
landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA340084
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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