Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy
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. Th...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1186383/full |
| _version_ | 1827932942218821632 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Wenshuai Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T07:16:33Z |
| format | Article |
| id | doaj.art-f045da456b054ea498725839ea03d3ed |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T07:16:33Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f045da456b054ea498725839ea03d3ed2023-06-05T05:21:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11863831186383Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapyWenshuai Li0Wenshuai Li1Xuanxuan Pan2Lirong Chen3Haoshu Cui4Shaocong Mo5Yida Pan6Yuru Shen7Menglin Shi8Jianlin Wu9Feifei Luo10Jie Liu11Na Li12State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, Macao SAR, ChinaDepartment of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, Macao SAR, ChinaDepartment of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, Macao SAR, ChinaAdoptive 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1186383/fullcell metabolismcancer therapyoptimization strategyCAR (chimeric antigen receptor) T cellsimmunity therapy |
| spellingShingle | 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 Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy Frontiers in Immunology cell metabolism cancer therapy optimization strategy CAR (chimeric antigen receptor) T cells immunity therapy |
| title | Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy |
| title_full | Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy |
| title_fullStr | Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy |
| title_full_unstemmed | Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy |
| title_short | Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy |
| title_sort | cell metabolism based optimization strategy of car t cell function in cancer therapy |
| topic | cell metabolism cancer therapy optimization strategy CAR (chimeric antigen receptor) T cells immunity therapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1186383/full |
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