BATF-mediated regulation of exhausted CD8+ T-cell responses and potential implications for chimeric antigen receptor-T therapy

Immunotherapy. 2024 Mar;16(5):331-340. doi: 10.2217/imt-2023-0170. Epub 2024 Jan 24.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy for malignant tumors has reached a crucial stage, with recent studies underscoring the role of T-cell exhaustion in determining the efficacy of CAR-T therapy. This trailblazing discovery has opened new avenues to augment the potency of CAR-T therapy. Basic leucine zipper ATF-like transcription factor (BATF) is indispensable in alleviating T-cell exhaustion and is pivotal in the early stages of CD8+ T-cell differentiation. In cooperation with other transcription factors, it plays a key role in the differentiation and maturation processes of exhausted T cells. A deeper comprehension of BATF's mechanisms in T-cell biology may yield novel insights into amplifying the efficacy of CAR-T therapy.

Keywords: BATF; CD8+ T-cell differentiation; T-cell exhaustion; T-cell therapy; amplifying CAR-T efficacy; chimeric antigen receptor; efficacy; malignant tumors; potency; transcription factor.

Plain language summary

Chimeric antigen receptor (CAR) T-cell therapy, a treatment that boosts the body's immune system to fight cancer, has made significant progress. Recent research has shown that T-cell exhaustion, which is when the body's immune cells become less effective, affects how well this therapy works. This finding has opened new possibilities to make CAR-T therapy more effective. There is a specific protein called BATF that plays an important role in reducing T-cell exhaustion and influencing the early development of certain immune cells. This review describes how BATF interacts with exhausted T cells, to improve CAR-T therapy. By understanding how BATF works in the immune system, new ways to enhance CAR-T therapy and its ability to fight cancer may be found.

Publication types

  • Review

MeSH terms

  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • CD8-Positive T-Lymphocytes
  • Gene Expression Regulation
  • Humans
  • Immunotherapy, Adoptive
  • Receptors, Chimeric Antigen* / genetics
  • Transcription Factors

Substances

  • Receptors, Chimeric Antigen
  • Basic-Leucine Zipper Transcription Factors
  • Transcription Factors
  • BATF protein, human