Functional Characterization and Modeling of Acquired Resisance to Immune Modulation in Lung Cancer
Abstract
Immune checkpoint inhibitors are increasingly being used in the clinic to treat patients with advanced lung cancer. Even when these agents are effective, acquired resistance to immune checkpoint inhibitors can occur and very little is known about the mechanisms of resistance to these agents. Through this grant, we investigated genomic and transcriptional mechanisms of resistance in patient specimens and identified new potential mechanisms affecting antigen presentation, interferon signaling and other pathways that can affect innate immune cells and exclude immune cells from tumors. We also optimized immunocompetent mouse models to study resistance and to validate mechanisms in vivo including loss of b2-microglobulin and the tumor suppressor gene Pten. Finally, we investigated mechanisms to overcome resistance using these models
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2019
- Accession Number
- AD1095244
Entities
People
- Katerina Politi
Organizations
- Yale University