PT  - JOURNAL ARTICLE
AU  - Frederick S. Varn
AU  - Yue Wang
AU  - Chao Cheng
TI  - Genomic characterization of six virus-associated cancers identifies changes in the tumor microenvironment and altered genetic programming
AID  - 10.1101/289900
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 289900
4099  - http://biorxiv.org/content/early/2018/04/21/289900.short
4100  - http://biorxiv.org/content/early/2018/04/21/289900.full
AB  - Viruses affect approximately 20% of all human cancers and induce the expression of viral oncoproteins that make these tumors potent targets for immune checkpoint inhibitors. In this study, we apply computational tools to The Cancer Genome Atlas and other datasets to define how virus infection shapes the tumor microenvironment and genetic architecture of 6 virus-associated tumor types. Across cancers, the cellular composition of the microenvironment varied by viral status, with infected tumors often exhibiting increased infiltration of cytolytic cell types. Analyses of the infiltrating T cell receptor repertoire revealed that Epstein-Barr virus was associated with decreased diversity in multiple cancers, suggesting an antigen-driven immune response. Tissue-specific gene expression signatures capturing these virus-induced transcriptomic changes successfully predicted virus status in independent datasets and were associated with both immune- and proliferation-related features that were predictive of prognosis. The analyses presented suggest viruses have distinct effects in different tumors with implications for immunotherapy.