Pan-cancer proteogenomics characterization of tumor immunity.

Despite the successes of immunotherapy in cancer treatment over recent decades, less than <10%–20% cancer cases have demonstrated durable responses from immune checkpoint blockade. To enhance the efficacy of immunotherapies, combination therapies suppressing multiple immune evasion mechanisms are increasingly contemplated. To better understand immune cell surveillance and diverse immune evasion responses in tumor tissues, we comprehensively characterized the immune landscape of more than 1,000 tumors across ten different cancers using CPTAC pan-cancer proteogenomic data. We identified seven distinct immune subtypes based on integrative learning of cell type compositions and pathway activities. We then thoroughly categorized unique genomic, epigenetic, transcriptomic, and proteomic changes associated with each subtype. Further leveraging the deep phosphoproteomic data, we studied kinase activities in different immune subtypes, which revealed potential subtype-specific therapeutic targets. Insights from this work will facilitate the development of future immunotherapy strategies and enhance precision targeting with existing agents. [Display omitted] • Proteogenomics reveals seven immune subtypes spanning 10 cancer types • DNA alterations associate with immune subtypes and affect proteomic profiles • Kinase activation in immune subtypes suggests potential therapeutic targets • Digital pathology reveals infiltrating cells associated with immune subtypes Immunotherapy holds strong promise for cancer treatment but at present benefits only a small proportion of cases. A pan-cancer analysis of the immune landscape in more than 1,000 tumors across ten cancer types reveals immune surveillance and immune evasion mechanisms as well as potential molecular target that could augment future immunotherapy and precision medicine strategies. [ABSTRACT FROM AUTHOR]