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Defining 'T cell exhaustion'.

Christian U Blank1, W Nicholas Haining2, Werner Held3

  • 1Netherlands Cancer Institute, Amsterdam, Netherlands. c.blank@nki.nl.

Nature Reviews. Immunology
|October 2, 2019
PubMed
Summary
This summary is machine-generated.

T cell exhaustion, a state of T cell dysfunction, has diverse definitions across chronic infections and tumors. Experts highlight distinct TCF1-negative exhausted cells and self-renewing TCF1-positive cells, with TOX driving epigenetic changes.

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Area of Science:

  • Immunology
  • Cellular Biology
  • Cancer Research

Background:

  • T cell exhaustion is a critical factor in chronic infections and cancer immunity.
  • Understanding T cell exhaustion is vital for improving immunotherapies like checkpoint blockade and T cell transfer.
  • Existing definitions of T cell exhaustion vary, impacting therapeutic strategies.

Purpose of the Study:

  • To consolidate expert opinions on the definition and characteristics of T cell exhaustion.
  • To explore the heterogeneity of exhausted T cells, including TCF1-positive and TCF1-negative populations.
  • To discuss the role of transcriptional regulator TOX in the epigenetic regulation of T cell exhaustion.

Main Methods:

  • Expert consensus-building viewpoint article.
  • Review of recent scientific literature on T cell exhaustion.
  • Discussion of key molecular regulators, such as TOX and TCF1.

Main Results:

  • Expert definitions of T cell exhaustion range from complete loss of function to altered function preventing immunopathology.
  • A dichotomy exists between terminally differentiated TCF1-negative exhausted T cells and self-renewing TCF1-positive T cells.
  • The transcriptional regulator TOX is implicated in the epigenetic enforcement of T cell exhaustion.

Conclusions:

  • Clarifying T cell exhaustion definitions is crucial for effective cancer and infectious disease immunotherapies.
  • TCF1-positive cells may possess stem-like properties, but their developmental relationship to exhausted cells requires further investigation.
  • Reversing epigenetic exhaustion and understanding its impact on T cell persistence are key future research directions.