T-cell exhaustion in CAR-T-cell therapy and strategies to overcome it

Immunology. 2023 Aug;169(4):400-411. doi: 10.1111/imm.13642. Epub 2023 Mar 20.

Abstract

Tumour immunotherapy has achieved good therapeutic effects in clinical practice and has received increased attention. Cytotoxic T cells undoubtedly play an important role in tumour immunotherapy. As a revolutionary tumour immunotherapy approach, chimeric antigen receptor T-cell (CAR-T-cell) therapy has made breakthroughs in the treatment of haematological cancers. However, T cells are easily exhausted in vivo, especially after they enter solid tumours. The exhaustion of T cells can lead to poor results of CAR-T-cell therapy in the treatment of solid tumours. Here, we review the reasons for T-cell exhaustion and how T-cell exhaustion develops. We also review and discuss ways to improve CAR-T-cell therapy effects by regulating T-cell exhaustion.

Keywords: CAR-T-cell therapy; T-cell exhaustion; immunotherapy.

Publication types

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

MeSH terms

  • Cell- and Tissue-Based Therapy
  • Humans
  • Immunotherapy, Adoptive / methods
  • Neoplasms*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Chimeric Antigen* / genetics
  • T-Cell Exhaustion

Substances

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