Integrated Genomic Characterization of the Human Immunome in Cancer.
Erxi Wu, Ph.D.
Li, Y., Burgman, B., McGrail, D.J., Sun, M., Qi, D., Shukla, S.A., Wu, E., Capasso, A., Lin, S.Y., Wu, C.J., Eckhardt, S.G., Mills, G.B., Li, B., Sahni, N. and Yi, S.S. (2020). “Integrated Genomic Characterization of the Human Immunome in Cancer.” Cancer Res Aug 27;canres.0384.2020. [Epub ahead of print.].
Alterations in immune-related pathways are common hallmarks of cancer. A comprehensive understanding of how cancer mutations rewire immune signaling networks and functional output across cancer types is instrumental to realize the full potential of immunotherapy. Here we systematically interrogated somatic mutations involved in immune signaling that alter immune responses in cancer patients. To do so, we developed a Network-based Integrative model to Prioritize Potential immune respondER genes (NIPPER). Identified mutations were enriched in essential protein domains and genes identified by NIPPER were associated with responsiveness to multiple immunotherapy modalities. These genes were used to devise an interactome network propagation framework integrated with drug-associated gene signatures to identify potential immunomodulatory drug candidates. Together, our systems-level analysis results help interpret the heterogeneous immune responses among patients and serve as a resource for future functional studies and targeted therapeutics.