Single-cell RNA-sequencing of human CD8+ T cells reveals signatures that determine antigen specificity in cancer immunotherapy 9180

Abstract Description CD8+ T cells are key players in various cancer therapies, including adoptive cell transfer (ACT) and tumor infiltrating lymphocyte (TIL) therapy. However, not all CD8+ T cells in the tumor microenvironment (TME) exhibit specificity for cancer antigens, regardless of their initial activation. To elucidate which factors drive the antigen specificity, we performed single-cell RNA sequencing (scRNA-seq) on IFNγ-secreting MART-1 tetramer-positive and -negative cells. For this, CD8+ T cells were activated twice with peptide-loaded monocyte-derived dendritic cells (mo-DCs) and sorted out based on the tetramer staining. We found that the genes regulating phosphatidylinositol 3-kinase (PI3K)/Akt pathway were differentially expressed in tetramer-positive and -negative groups. To explicate how the differential gene expressions are regulated, we conducted further analysis and identified genes that were significantly highly expressed in either group and are in the process of determining how the regulation of these genes would affect antigen specificity and hence the function of CD8+ T cells to target cancer. Collectively, these findings could be used not only in cancer immunotherapy to increase cancer specific CD8+ T cells by modulating antigen specificity-determining factors to turn cold tumors into hot tumors, but also in regulating antigen-independent activation of CD8+ T cells, which can lead to off-target effects. Funding Sources This research was supported by Korea Research Institute of Bioscience and Biotechnology (KRIBB), Research Initiative Program; KGM9992521. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)