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.

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.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 16, No. 5

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Received 27 July 2023

Accepted 2 January 2024

Published online 24 January 2024

Published in print March 2024

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Author contributions

S Chao conducted the search of Pubmed and drafted the manuscript. W Zhengxin supervised the project, provided critical feedback and revised the manuscript. L Dan contributed to verifying the accuracy of the content and provided in-depth guidance on the writing of this paper.

Financial disclosure

This study was supported by grants from the National Natural Science Foundation of China (81873874 and 82071797), Clinical Research Plan of SHDC (no. SHDC2020CR2021B and SHDC2020CR5012) and the National Key Research and Development Program of China (grant no. 2023YFC2505900). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was used in the production of this manuscript.

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

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Reference

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