T-cell exhaustion in the tumor microenvironment

Cell Death Dis. 2015 Jun 18;6(6):e1792. doi: 10.1038/cddis.2015.162.


T-cell exhaustion was originally identified during chronic infection in mice, and was subsequently observed in humans with cancer. The exhausted T cells in the tumor microenvironment show overexpressed inhibitory receptors, decreased effector cytokine production and cytolytic activity, leading to the failure of cancer elimination. Restoring exhausted T cells represents an inspiring strategy for cancer treatment, which has yielded promising results and become a significant breakthrough in the cancer immunotherapy. In this review, we overview the updated understanding on the exhausted T cells in cancer and their potential regulatory mechanisms and discuss current therapeutic interventions targeting exhausted T cells in clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Cytokines / metabolism
  • Humans
  • Lymphocyte Activation / immunology
  • Mice
  • NFATC Transcription Factors / metabolism
  • Neoplasms / immunology*
  • Positive Regulatory Domain I-Binding Factor 1
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism
  • Repressor Proteins / metabolism
  • T-Box Domain Proteins / metabolism
  • T-Lymphocytes / immunology*
  • Tumor Escape / immunology*
  • Tumor Microenvironment / immunology*


  • BATF protein, human
  • Basic-Leucine Zipper Transcription Factors
  • Cytokines
  • NFATC Transcription Factors
  • NFATC1 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Repressor Proteins
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • PRDM1 protein, human
  • Positive Regulatory Domain I-Binding Factor 1