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CRISPR 筛选在肿瘤发生、肿瘤耐药与肿瘤免疫治疗机制研究中的应用

英文原题:Application of CRISPR screen in mechanistic studies of tumor development, tumor drug resistance, and tumor immunotherapy.

查看英文原题

Application of CRISPR screen in mechanistic studies of tumor development, tumor drug resistance, and tumor immunotherapy.

PubMed 2023/06/23(内容时间) Front Cell Dev Biol Q1 · IF 5.3(JCR 2025)

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中文摘要

肿瘤是人类健康的最大威胁之一。尽管近几十年来技术和研究的进步极大地推动了肿瘤治疗的发展,但仍远未达到预期。因此,探索肿瘤生长、转移和耐药的机制具有重要意义。基于成簇规律间隔短回文重复序列(CRISPR)-CRISPR相关蛋白(Cas)9基因编辑技术的筛选是探索上述方面的有力工具。本综述总结了近期在肿瘤细胞和肿瘤微环境中免疫细胞中进行的筛选研究。肿瘤细胞中的筛选主要集中于探索肿瘤细胞生长、转移以及肿瘤细胞如何逃避FDA批准药物或免疫治疗的机制。而肿瘤相关免疫细胞中的研究主要旨在鉴定能够增强细胞毒性T淋巴细胞(CTLs)、CAR-T 细胞和巨噬细胞抗肿瘤功能的信号通路。

此外,我们讨论了CRISPR筛选的局限性、优势,并进一步探讨其在肿瘤研究中的未来应用。重要的是,近期高通量肿瘤相关CRISPR筛选的进展深刻促进了肿瘤发生、肿瘤耐药和肿瘤免疫治疗的新概念和机制,这些最终将有助于肿瘤患者的临床治疗。

展开英文摘要原文

Tumor is one of the biggest threats to human health. Though tumor therapy has been dramatically advanced by the progress of technology and research in recent decades, it is still far from expectations.

Thus, it is of great significance to explore the mechanisms of tumor growth, metastasis, and resistance. Screen based on Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated protein (Cas) 9 gene editing technology are powerful tools for exploring the abovementioned facets. This review summarizes the recent screen performed in cancer cells and immune cells in the tumor microenvironment.

The screens in cancer cells mainly focus on exploring the mechanisms underlying cancer cells' growth, metastasis, and how cancer cells escape from the FDA approved drugs or immunotherapy. And the studies in tumor-associated immune cells are primarily aimed at identifying signaling pathways that can enhance the anti-tumor function of cytotoxic T lymphocytes (CTLs), CAR-T cells, and macrophages.

Moreover, we discuss the limitations, merits of the CRISPR screen, and further its future application in tumor studies.

Importantly, recent advances in high throughput tumor related CRISPR screen have deeply contributed to new concepts and mechanisms underlying tumor development, tumor drug resistance, and tumor immune therapy, all of which will eventually potentiate the clinical therapy for tumor patients.

论文信息

作者
Li M、Sun J、Shi G
第一作者单位
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of Chinese Academy of Sciences, Shanghai, China.China
通讯作者单位
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.China
文献类型
综述
期刊
Frontiers in cell and developmental biology2023
原文标识
PubMed 37427373 · DOI 10.3389/fcell.2023.1220376