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

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

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

Front Immunol. 2023 Jun 5:14:1186383. doi: 10.3389/fimmu.2023.1186383. eCollection 2023.

Authors

Wenshuai Li^{1

2}, Xuanxuan Pan², Lirong Chen², Haoshu Cui², Shaocong Mo², Yida Pan², Yuru Shen², Menglin Shi², Jianlin Wu¹, Feifei Luo², Jie Liu², Na Li¹

Affiliations

¹ State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, Macao SAR, China.
² Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China.

Abstract

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.

Keywords: CAR (chimeric antigen receptor) T cells; cancer therapy; cell metabolism; immunity therapy; optimization strategy.

Publication types

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

MeSH terms

Hematologic Neoplasms* / metabolism
Humans
Immunotherapy, Adoptive
Neoplasms*
Receptors, Chimeric Antigen*
T-Lymphocytes
Tumor Microenvironment

Substances

Receptors, Chimeric Antigen

Grants and funding

This work was supported by a grant from the National Natural Science Foundation of China (Project code: 82121002) and Macao Young Scholars Program (Project code: AM2020022).