Targeting dsRNA Pathways Enhances Immunotherapy

Example 3

Deletion of novel candidate immunotherapy targets was found to increase sensitivity of tumor cells to immunotherapy. sgRNAs targeting genes involved in dsRNA editing, sensing, and/or metabolism (e.g., Adar) were markedly depleted in mice treated with GVAX and PD-1 blockade (FIG. 2) relative to growth in TCRα^−/− mice. In many cases, multiple members of the same pathway or even the same multi-protein complex were depleted under immune selective pressure, underscoring the importance of diverse biological pathways, such as the dsRNA editing, sensing, and/or metabolism pathway (FIGS. 3-7).