How metabolism bridles cytotoxic CD8 + T cells through epigenetic modifications

Trends Immunol. 2021 May;42(5):401-417. doi: 10.1016/ Epub 2021 Apr 15.


In the direct competition for metabolic resources between cancer cells and tumor-infiltrating CD8+ T cells, the latter are bound to lose out. These effector lymphocytes are therefore rendered exhausted or dysfunctional. Emerging insights into the mechanisms of T cell unresponsiveness in the tumor microenvironment (TME) point towards epigenetic mechanisms as crucial regulatory factors. In this review, we discuss the effects of characteristic components of the TME, i.e. glucose/amino acid dearth with elevated levels of reactive oxygen species (ROS), on DNA methylation and histone modifications in CD8+ T cells. We then take a closer look at the translational potential of epigenetic interventions that aim to improve current immunotherapeutic strategies, including the adoptive transfer of T cell receptor (TCR) or chimeric antigen receptor (CAR) engineered T cells.

Publication types

  • Review

MeSH terms

  • CD8-Positive T-Lymphocytes*
  • Epigenesis, Genetic
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen*
  • Tumor Microenvironment


  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen