LaFleur Martin W, Sharpe Arlene H
Department of Immunology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Annu Rev Cancer Biol. 2022 Apr;6:103-122. doi: 10.1146/annurev-cancerbio-070120-094725. Epub 2021 Dec 23.
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.
癌症免疫疗法，如免疫检查点阻断（ICB），已被广泛应用于多种肿瘤类型，并带来了巨大的临床益处。然而，ICB并非对所有患者都有效，而且将ICB与其他基于免疫的疗法联合使用的尝试也未达到最初的预期。因此，迫切需要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患者。系统生物学方法非常适合解决这一问题，因为这些方法能够同时评估多个基因靶点，并对它们对于感兴趣的表型的相对重要性进行排序。因此，功能丧失型CRISPR筛选是一组新兴的工具，用于对调节肿瘤和免疫细胞中感兴趣的通路的基因靶点进行优先级排序。本综述描述了为发现癌症免疫疗法靶点而进行的首次筛选，以及将推动下一代筛选的技术进展。
