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.

中文翻译：

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通过无偏CRISPR / Cas9筛选确定的关键癌症脆弱性可为有效的癌症免疫疗法提供信息

人类癌症的突变情况非常复杂。尽管下一代测序的目的是对肿瘤细胞中的体细胞变化进行全面分类，但它无法从驾驶员突变中区分出驾驶员。功能基因组学方法，特别是CRISPR / Cas9，可实现基因发现和基因功能注释。确实，最近的CRISPR / Cas9技术蓬勃发展，开发出了更先进，更通用的平台，能够对基因进行基因敲除，从而对单个核苷酸碱基进行高通量的全基因组编辑。随着新平台的不断涌现，导航可用的CRISPR工具以及如何有效地使用它们来理解癌症生物学可能是一个挑战。这篇综述概述了当前和新兴的CRISPR技术及其在癌症建模和确定新疗法中的作用。具体而言，将讨论如何通过鉴定肿瘤内在和外在机制逃避免疫识别来利用CRISPR筛选方法来增强免疫疗法。