Rewiring mitochondrial metabolism to counteract exhaustion of CAR-T cells

J Hematol Oncol. 2022 Mar 28;15(1):38. doi: 10.1186/s13045-022-01255-x.


Short persistence and early exhaustion of T cells are major limits to the efficacy and broad application of immunotherapy. Exhausted T and chimeric antigen receptor (CAR)-T cells upregulate expression of genes associated with terminated T cell differentiation, aerobic glycolysis and apoptosis. Among cell exhaustion characteristics, impaired mitochondrial function and dynamics are considered hallmarks. Here, we review the mitochondrial characteristics of exhausted T cells and particularly discuss different aspects of mitochondrial metabolism and plasticity. Furthermore, we propose a novel strategy of rewiring mitochondrial metabolism to emancipate T cells from exhaustion and of targeting mitochondrial plasticity to boost CAR-T cell therapy efficacy.

Keywords: CAR-T cell exhaustion; Metabolism; Mitochondria; Single-cell techniques.

Publication types

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

MeSH terms

  • Humans
  • Immunotherapy
  • Immunotherapy, Adoptive*
  • Lymphocyte Activation
  • Mitochondria / metabolism
  • T-Lymphocytes*