Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy

Wenshuai Li; Wenshuai Li; Xuanxuan Pan; Lirong Chen; Haoshu Cui; Shaocong Mo; Yida Pan; Yuru Shen; Menglin Shi; Jianlin Wu; Feifei Luo; Jie Liu; Na Li

doi:10.3389/fimmu.2023.1186383

Frontiers in Immunology (Jun 2023)

Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy

Wenshuai Li,
Wenshuai Li,
Xuanxuan Pan,
Lirong Chen,
Haoshu Cui,
Shaocong Mo,
Yida Pan,
Yuru Shen,
Menglin Shi,
Jianlin Wu,
Feifei Luo,
Jie Liu,
Na Li

Affiliations

Wenshuai Li: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, Macao SAR, China
Wenshuai Li: Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China
Xuanxuan Pan: Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China
Lirong Chen: Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China
Haoshu Cui: Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China
Shaocong Mo: Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China
Yida Pan: Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China
Yuru Shen: Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China
Menglin Shi: Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China
Jianlin Wu: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, Macao SAR, China
Feifei Luo: Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China
Jie Liu: Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China
Na Li: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, Macao SAR, China

DOI: https://doi.org/10.3389/fimmu.2023.1186383
Journal volume & issue: Vol. 14

Abstract

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Adoptive cell therapy (ACT) using chimeric antigen receptor (CAR)-modified T cells has revolutionized the field of immune-oncology, showing remarkable efficacy against hematological malignancies. However, its success in solid tumors is limited by factors such as easy recurrence and poor efficacy. The effector function and persistence of CAR-T cells are critical to the success of therapy and are modulated by metabolic and nutrient-sensing mechanisms. Moreover, the immunosuppressive tumor microenvironment (TME), characterized by acidity, hypoxia, nutrient depletion, and metabolite accumulation caused by the high metabolic demands of tumor cells, can lead to T cell “exhaustion” and compromise the efficacy of CAR-T cells. In this review, we outline the metabolic characteristics of T cells at different stages of differentiation and summarize how these metabolic programs may be disrupted in the TME. We also discuss potential metabolic approaches to improve the efficacy and persistence of CAR-T cells, providing a new strategy for the clinical application of CAR-T cell therapy.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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