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 effec-tiveness.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.
Shasha Liu;Yuyu Zhao;Yaoxin Gao;Feng Li;Yi Zhang
Biotherapy Center and Cancer Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,ChinaBiotherapy Center and Cancer Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China||School of Life Sciences,Zhengzhou University,Zhengzhou,Henan 450052,ChinaBiotherapy Center and Cancer Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China||Engineering Key Laboratory for Cell Therapy of Henan Province,Zhengzhou,Henan 450052,ChinaBiotherapy Center and Cancer Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China||School of Life Sciences,Zhengzhou University,Zhengzhou,Henan 450052,China||Engineering Key Laboratory for Cell Therapy of Henan Province,Zhengzhou,Henan 450052,China||School of Public Health,Zhengzhou University,Zhengzhou,Henan 450000,China
CAR-T cell therapy;Metabolism;Tumor microenvironment;Immunotherapy;Mitochondrial fitness
《中华医学杂志（英文版）》 2024 (008)
909-920 / 12
This work was supported by grants from National Key Research and Development Program Intergovernmental Key Project for International Science and Technology Innovation Cooperation(No.2022YFE0141000),Natural Science Foundation of China(No.82203548),China Postdoctoral Science Foundation Project(No.2022M712894),Medical Science and Technology Project of Henan Province(No.LHGJ20220385),and Major science and technology project of Henan Province(No.221100310100).
10.1097/CM9.0000000000003046
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