Abstract
RNA interference and CRISPR/Cas9 technologies now enable systematic discovery of genes that regulate key pathways in the complex interaction between immune cells and tumor cells. Discovery screens are feasible in an in vivo setting, allowing identification of genes that limit the effectiveness of anti-tumor immunity. In vivo discovery screens can be informed by single-cell RNA-seq experiments that define the differentially expressed genes between functionally distinct immune cell subpopulations, both in humans and relevant animal models. Novel targets for cancer immunotherapy are being defined by the in depth functional annotation of immunosuppressive pathways in the tumor microenvironment.