CRISPR Screens to Identify Regulators of Tumor Immunity.

Abstract

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.