CRISPR Screens to Identify Regulators of Tumor Immunity.

CRISPR Screens to Identify Regulators of Tumor Immunity.
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DOI:
10.1146/annurev-cancerbio-070120-094725
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发表时间:
2022-04
影响因子:
7.7
通讯作者:
Sharpe, Arlene H.
Sharpe, Arlene H.
中科院分区:
医学2区
文献类型:
--
作者:
LaFleur, Martin W.;Sharpe, Arlene H.

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癌症免疫疗法,如免疫检查点阻断(ICB),已广泛应用于各种肿瘤类型,具有巨大的临床效益。然而,ICB并不是对所有患者都有效,并且将ICB与其他基于免疫的疗法结合使用的尝试也没有达到最初的预期。因此,发现新的靶点和联合疗法以将免疫疗法的益处扩展到更多的患者,这是一个重大的未满足的需求。系统生物学方法非常适合解决这个问题,因为这些方法可以同时评估许多基因靶点,并对感兴趣的表型排序它们的相对重要性。因此,功能缺失CRISPR筛选是一套新兴的工具,用于优先调节肿瘤和免疫细胞中感兴趣的途径的基因靶标。这篇综述描述了发现癌症免疫治疗靶点的第一次筛查,以及将使下一代筛查成为可能的技术进步。
Cancer immunotherapies, such as immune checkpoint blockade (ICB), have been used in a wide range of tumor types with immense clinical benefit. However, ICB does not work in all patients, and attempts to combine ICB with other immune-based therapies have not lived up to their initial promise. Thus, there is a significant unmet need to discover new targets and combination therapies to extend the benefits of immunotherapy to more patients. Systems biology approaches are well suited for addressing this problem because these approaches enable evaluation of many gene targets simultaneously and ranking their relative importance for a phenotype of interest. As such, loss-of-function CRISPR screens are an emerging set of tools being used to prioritize gene targets for modulating pathways of interest in tumor and immune cells. This review describes the first screens performed to discover cancer immunotherapy targets and the technological advances that will enable next-generation screens.
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