Abstract 3384: Genome-wide epigenetic and transcriptional comparison of CD8 T cell functional states between mouse models of cancer and chronic viral infection

Abstract

Abstract Recent studies in mouse models of cancer and chronic viral infection applied genomic assays to profile various states of impaired T cell function and demonstrated that T cell dysfunction is epigenetically imprinted. However, comprehensive characterization of T cell dysfunction across models based on their epigenetic and transcriptional profiles is lacking. We reanalyzed a large collection of recently published chromatin accessibility (ATAC-seq) and gene expression (RNA-seq) data sets. After batch effect correction, we observed that epigenetic profiles of dysfunctional tumor-infiltrating T cells and exhausted T cells in chronic viral infection were surprisingly extremely similar. Furthermore, we observed that temporal progression towards dysfunction in chronic infection resembles that in tumorigenesis, and found that T cells committed to becoming dysfunctional early after activation. Motif analysis using generalized linear modeling allowed us to find candidate transcription factors associated with development of dysfunction in both immune settings. This analysis provides a better systematic understanding of cell-intrinsic mechanisms driving different functional states of CD8 T cells and demonstrates the power of systems biology approaches in cancer immunology. Citation Format: Yuri Pritykin, Christina Leslie. Genome-wide epigenetic and transcriptional comparison of CD8 T cell functional states between mouse models of cancer and chronic viral infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3384.