Integrated Genomic Characterization of the Human Immunome in Cancer
Abstract
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 patients with cancer. 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 01, 2020
- Source ID
- 10.1158/0008-5472.can-20-0384
Entities
People
- Anna Capasso
- Bo Li
- Brandon Burgman
- Catherine J Wu
- Dan Qi
- Daniel J. Mcgrail
- Erxi Wu
- Gordon B. Mills
- Ming Sun
- Nidhi Sahni
- S. Gail Eckhardt
- Sachet A Shukla
- Shiaw-Yih Lin
- Song Yi
- Yongsheng Li
Organizations
- Baylor College of Medicine
- Baylor Scott & White Health
- Cancer Prevention and Research Institute of Texas
- Harvard Medical School
- National Cancer Institute
- National Institutes of Health
- Oregon Health & Science University
- Ovarian Cancer Research Alliance
- Susan G. Komen for the Cure
- United States Department of Defense
- University of Texas Southwestern Medical Center
- University of Texas at Austin