Targeting metabolism to improve CAR-T cells therapeutic efficacy
10.1097/CM9.0000000000003046
- VernacularTitle:Targeting metabolism to improve CAR-T cells therapeutic efficacy
- Author:
Shasha LIU
1
;
Yuyu ZHAO
;
Yaoxin GAO
;
Feng LI
;
Yi ZHANG
Author Information
1. Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Keywords:
CAR-T cell therapy;
Metabolism;
Tumor microenvironment;
Immunotherapy;
Mitochondrial fitness
- From:
Chinese Medical Journal
2024;137(8):909-920
- CountryChina
- Language:Chinese
-
Abstract:
Chimeric antigen receptor T (CAR-T) cell therapy achieved advanced progress in the treatment of hematological tumors. However, the application of CAR-T cell therapy for solid tumors still faces many challenges. Competition with tumor cells for metabolic resources in an already nutrient-poor tumor microenvironment is a major contributing cause to CAR-T cell therapy’s low effectiveness. Abnormal metabolic processes are now acknowledged to shape the tumor microenvironment, which is characterized by increased interstitial fluid pressure, low pH level, hypoxia, accumulation of immunosuppressive metabolites, and mitochondrial dysfunction. These factors are important contributors to restriction of T cell proliferation, cytokine release, and suppression of tumor cell-killing ability. This review provides an overview of how different metabolites regulate T cell activity, analyzes the current dilemmas, and proposes key strategies to reestablish the CAR-T cell therapy’s effectiveness through targeting metabolism, with the aim of providing new strategies to surmount the obstacle in the way of solid tumor CAR-T cell treatment.
