用于癌症免疫治疗策略开发的CRISPR筛选技术进展。

Advancements in CRISPR screens for the development of cancer immunotherapy strategies.

作者信息

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

机构信息

Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.

出版信息

Mol Ther Oncolytics. 2023 Oct 5;31:100733. doi: 10.1016/j.omto.2023.100733. eCollection 2023 Dec 19.

DOI:10.1016/j.omto.2023.100733

PMID:37876793

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10591018/

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.

摘要

CRISPR筛选技术通过使用CRISPR-Cas9系统干扰基因表达，实现对基因功能的系统性和可扩展性研究。在癌症免疫治疗领域，该技术助力发现了调控肿瘤发生发展、免疫反应性以及免疫治疗干预效果的基因、生物标志物和信号通路。通过进行大规模基因筛选，研究人员成功鉴定出了新的靶点，以抑制肿瘤生长、增强抗肿瘤免疫反应，并克服肿瘤微环境（TME）中的免疫抑制。在此，我们概述了为鉴定新治疗靶点而在肿瘤细胞中进行的CRISPR筛选。我们还探讨了CRISPR筛选在免疫细胞中的应用，以推动包括T细胞、自然杀伤细胞、树突状细胞和巨噬细胞在内的细胞疗法的发展。此外，我们概述了成功实施免疫特异性CRISPR筛选所需的关键组成部分，并探索了未来研究的潜在方向。