Discovery of Tissue-specific Gene Expression Patterns in CD8 T Cells by Single-cell RNA-seq

Ying Zheng⁰, Di Yu¹, Jiayu Wen⁰
(0) Australian National University
(1) The University of Queensland

Find me on Wed Nov 25th, 1:30-2:50pm AEDT in Remo, table 104

Abstract
The current most effective clinical cancer treatment, immune checkpoint blockade (ICB), has been argued to be the basis of next-generation immunotherapy. Nevertheless, although the efficacy of ICB has been attributed to CD8 T cells, the underlying precise mechanism remains poorly understood. In recent years, with the clinical application of ICB, the distinct effects of ICB on the treatment of different cancer types and the tissue-specific complications of ICB (immune-related adverse events, irAEs) have been widely reported. In allusion to the widely reported association between tissues and ICB effects, in this research, we used single-cell technologies to profile murine tissue-infiltrating CD8 T cells obtained from 8 different tissues, including the small intestine, kidney, liver, lymph nodes, lung, PBMCs, spinal cord, and spleen. We comprehensively compared and characterised tissue-infiltrating CD8 T cells to explore tissue-specific gene expression patterns. Our research proves cellular heterogeneity of tissue-infiltrating CD8 T cells, profiles their abundant tissue-specific gene expression patterns, and most importantly, identifies several tissue-specific-infiltrating CD8 T cell subpopulations in the liver, kidney, and small intestine. The trajectory analysis reveals the distinct differentiation statuses of infiltrating CD8 T cells across tissues and identified subpopulations. The pathway enrichment analysis further highlights the immune-related mechanisms involving detected tissue-specific gene expression patterns. These discoveries have important implications for illustrating the underlying association between tissues and ICB, including the relationship between tissue-specific irAEs and ICB effects in different cancer types.