articleProceedings of the National Academy of SciencesMay 31, 2019BRONZE OA

TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8 + T cell exhaustion

HSHyungseok SeoJCJoyce ChenEGEdahí González‐AvalosDSDaniela Samaniego‐CastruitaADArundhoti Das

La Jolla Institute for Immunology · University of California San Diego · +5 more institutions

PubMed
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Abstract

T cells expressing chimeric antigen receptors (CAR T cells) have shown impressive therapeutic efficacy against leukemias and lymphomas. However, they have not been as effective against solid tumors because they become hyporesponsive (“exhausted” or “dysfunctional”) within the tumor microenvironment, with decreased cytokine production and increased expression of several inhibitory surface receptors. Here we define a transcriptional network that mediates CD8 + T cell exhaustion. We show that the high-mobility group (HMG)-box transcription factors TOX and TOX2, as well as members of the NR4A family of nuclear receptors, are targets of the calcium/calcineurin-regulated transcription factor NFAT, even in the…

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756
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Topics & keywords

Topics
Keywords
  • NFAT
  • Transcription factor
  • Cytotoxic T cell
  • Biology
  • Cytokine
  • CD8
  • T cell
  • Cancer research
UN Sustainable Development Goals
  • Good health and well-being
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