Abstract IA20: Chromatin state and scRNA-seq analysis defines a common differentiation trajectory towards T-cell exhaustion

We will describe a unified chromatin state and single cell expression analysis underlying T-cell differentiation to “exhaustion.” Numerous studies in chronic viral infection and tumor models have shown that most T cells progress to a terminally dysfunctional (“exhausted”) state from which they cannot be rescued by current immunotherapies. We performed a systematic analysis of over 280 ATAC-seq and RNA-seq experiments from eight published studies of CD8 T cell dysfunction, using a statistical batch correction to define a common differentiation trajectory to terminal exhaustion in all settings of chronic antigen exposure and to identify transcription factors involved in this progression. We further performed scRNA-seq analysis of CD8 T cells at multiple time points during acute and chronic viral infection and in adoptive cell transfer studies to elucidate this trajectory at single-cell resolution. Citation Format: Christina Leslie. Chromatin state and scRNA-seq analysis defines a common differentiation trajectory towards T-cell exhaustion [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr IA20.