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Functional CRISPR screens in T cells reveal new opportunities for cancer immunotherapies

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单位: [1]Department of Obstetrics and Gynecology,National Clinical Research Center for Obstetrics and Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China. [2]Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education),Hubei Key Laboratory of Tumor Invasion and Metastasis,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China. [3]Department of Plastic and Cosmetic Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China.
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关键词: CRISPR screen T cell Tumour immunity Cancer immunotherapy Adoptive cell therapy Immune checkpoint inhibitor T cell exhaustion

摘要:
T cells are fundamental components in tumour immunity and cancer immunotherapies, which have made immense strides and revolutionized cancer treatment paradigm. However, recent studies delineate the predicament of T cell dysregulation in tumour microenvironment and the compromised efficacy of cancer immunotherapies. CRISPR screens enable unbiased interrogation of gene function in T cells and have revealed functional determinators, genetic regulatory networks, and intercellular interactions in T cell life cycle, thereby providing opportunities to revamp cancer immunotherapies. In this review, we briefly described the central roles of T cells in successful cancer immunotherapies, comprehensively summarised the studies of CRISPR screens in T cells, elaborated resultant master genes that control T cell activation, proliferation, fate determination, effector function, and exhaustion, and highlighted genes (BATF, PRDM1, and TOX) and signalling cascades (JAK-STAT and NF-κB pathways) that extensively engage in multiple branches of T cell responses. In conclusion, this review bridged the gap between discovering element genes to a specific process of T cell activities and apprehending these genes in the global T cell life cycle, deepened the understanding of T cell biology in tumour immunity, and outlined CRISPR screens resources that might facilitate the development and implementation of cancer immunotherapies in the clinic.© 2024. The Author(s).

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出版当年[2023]版:
大类 | 1 区 医学
小类 | 1 区 生化与分子生物学 1 区 肿瘤学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 生化与分子生物学 1 区 肿瘤学
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出版当年[2022]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 ONCOLOGY
最新[2023]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

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第一作者单位: [1]Department of Obstetrics and Gynecology,National Clinical Research Center for Obstetrics and Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China. [2]Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education),Hubei Key Laboratory of Tumor Invasion and Metastasis,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China.
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通讯机构: [1]Department of Obstetrics and Gynecology,National Clinical Research Center for Obstetrics and Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China. [2]Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education),Hubei Key Laboratory of Tumor Invasion and Metastasis,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China.
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