Abstract B26: Genomic analysis of the virus-induced tumor microenvironment in six cancer types

Abstract

Abstract With the growing successes of immunotherapy, there is now a focus on identifying biomarkers that can predict response and long-term survival following treatment. The presence of immunogenic antigen proteins has been linked to improved response rates across patients receiving immune checkpoint inhibitors. However, these findings have been localized to melanoma and lung tumors which contain high mutation burdens and thus higher neoantigen loads. Viruses cause approximately 20% of all human cancers and are especially prevalent in head and neck cancers, cervical cancers, and liver cancers. Viral protein expression is another source of immunogenicity, making these tumor types potent targets for immune checkpoint inhibitors. Recent advances in genome-based immune profiling technologies have enabled the systematic characterization of the tumor microenvironment over large cohorts of patients. In this study, we apply several of these tools to The Cancer Genome Atlas and other datasets to define how virus infection shapes the tumor microenvironment of 6 virus-associated tumor types. Across all tissues studied, the cellular composition of the tumor microenvironment varied between tumors based on viral status, with infected tumors often exhibiting increased infiltration of cytolytic cell types. A gene expression signature capturing these virus-induced changes in the tumor microenvironment successfully predicted virus status in independent datasets and was associated with improved prognosis in head and neck cancer, indicating a protective role for virus-induced immune infiltration. To examine how viral gene expression affects the infiltrating T cell repertoire, T cell receptor diversity and abundance comparisons were made between viral and non-viral samples. The analyses presented here suggest virus infection is associated with a robust immune response. These findings have implications for precision medicine approaches to tumor immunotherapy. Citation Format: Frederick S. Varn, Dawei Li, Chao Cheng. Genomic analysis of the virus-induced tumor microenvironment in six cancer types [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B26.