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Advancements in CRISPR screens for the development of cancer immunotherapy strategies

Yan-Ruide Li, Zibai Lyu, Yanxin Tian, Ying Fang, Yichen Zhu, Yuning Chen, Lili Yang

2023Molecular Therapy — Oncolytics17 citationsDOIOpen Access PDF

Abstract

CRISPR screen technology enables systematic and scalable interrogation of gene function by using the CRISPR-Cas9 system to perturb gene expression. In the field of cancer immunotherapy, this technology has empowered the discovery of genes, biomarkers, and pathways that regulate tumor development and progression, immune reactivity, and the effectiveness of immunotherapeutic interventions. By conducting large-scale genetic screens, researchers have successfully identified novel targets to impede tumor growth, enhance anti-tumor immune responses, and surmount immunosuppression within the tumor microenvironment (TME). Here, we present an overview of CRISPR screens conducted in tumor cells for the purpose of identifying novel therapeutic targets. We also explore the application of CRISPR screens in immune cells to propel the advancement of cell-based therapies, encompassing T cells, natural killer cells, dendritic cells, and macrophages. Furthermore, we outline the crucial components necessary for the successful implementation of immune-specific CRISPR screens and explore potential directions for future research.

Topics & Concepts

CRISPRImmunotherapyImmune systemTumor microenvironmentBiologyComputational biologyGenome editingCancer immunotherapyCancerGeneCancer researchImmunologyGeneticsCRISPR and Genetic EngineeringCAR-T cell therapy researchImmune Cell Function and Interaction