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

Autor: Minghua Xiang, Huayi Li, Yuanyuan Zhan, Ding Ma, Qinglei Gao, Yong Fang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Molecular Cancer, Vol 23, Iss 1, Pp 1-28 (2024)
Druh dokumentu: article
ISSN: 1476-4598
DOI: 10.1186/s12943-024-01987-z
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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