The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
Eur J Immunol. 2020 Dec;50(12):1871-1884. doi: 10.1002/eji.202048712. Epub 2020 Dec 1.
The mutational landscape of human cancers is highly complex. While next generation sequencing aims to comprehensively catalogue somatic alterations in tumor cells, it fails to delineate driver from passenger mutations. Functional genomic approaches, particularly CRISPR/Cas9, enable both gene discovery, and annotation of gene function. Indeed, recent CRISPR/Cas9 technologies have flourished with the development of more sophisticated and versatile platforms capable of gene knockouts to high throughput genome wide editing of a single nucleotide base. With new platforms constantly emerging, it can be challenging to navigate what CRISPR tools are available and how they can be effectively applied to understand cancer biology. This review provides an overview of current and emerging CRISPR technologies and their power to model cancer and identify novel treatments. Specifically, how CRISPR screening approaches have been exploited to enhance immunotherapies through the identification of tumor intrinsic and extrinsic mechanisms to escape immune recognition will be discussed.
人类癌症的突变景观非常复杂。尽管下一代测序旨在全面描述肿瘤细胞中的体细胞改变，但它无法区分驱动突变和乘客突变。功能基因组方法，特别是 CRISPR/Cas9，可用于基因发现和基因功能注释。事实上，随着更复杂和多功能的平台的发展，能够进行基因敲除和高通量全基因组单核苷酸碱基编辑，最近的 CRISPR/Cas9 技术蓬勃发展。随着新平台的不断涌现，了解可用的 CRISPR 工具以及如何有效地应用它们来了解癌症生物学可能具有挑战性。本文综述了当前和新兴的 CRISPR 技术及其在模拟癌症和发现新疗法方面的强大功能。具体来说，将讨论如何通过识别肿瘤内在和外在的逃避免疫识别的机制，利用 CRISPR 筛选方法来增强免疫疗法。
