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.

中文翻译：

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T 细胞中的功能性 CRISPR 筛选揭示了癌症免疫疗法的新机遇

T 细胞是肿瘤免疫和癌症免疫疗法的基本组成部分，它们取得了巨大进步并彻底改变了癌症治疗模式。然而，最近的研究描绘了肿瘤微环境中T细胞失调的困境以及癌症免疫疗法疗效受损的困境。 CRISPR筛选能够对T细胞中的基因功能进行公正的询问，并揭示了T细胞生命周期中的功能决定因素、基因调控网络和细胞间相互作用，从而为改进癌症免疫疗法提供了机会。在这篇综述中，我们简要描述了T细胞在成功的癌症免疫治疗中的核心作用，全面总结了T细胞中CRISPR筛选的研究，详细阐述了控制T细胞激活、增殖、命运决定、效应功能和耗竭的主基因，并重点介绍了广泛参与 T 细胞反应多个分支的基因（BATF、PRDM1 和 TOX）和信号级联（JAK-STAT 和 NF-κB 通路）。总之，这篇综述弥合了发现 T 细胞活动特定过程的元件基因和在整体 T 细胞生命周期中理解这些基因之间的差距，加深了对肿瘤免疫中 T 细胞生物学的理解，并概述了 CRISPR 筛选可能的资源促进临床癌症免疫疗法的开发和实施。