Abstract

PD-L1 signaling is essential in regulating T cell function and keeping the balance of tumor microenvironment, but its role in modifying TCR-T cell cytotoxicity remains unknown. MART-1-specific TCR-T cells (TCR-TMART-1) were stimulated by MEL-526 tumor cells expressing different proportions of PD-L1 and used to perform cytotoxicity assays and single-cell RNA sequencing. Percentage changes of different specific cell clusters were analyzed. The percentage of cluster HLA-DR+CD38+CD8+ was upregulated after antigen stimulation, and tumor PD-L1 modified TCR-T cell function through downregulating the percentages of HLA-DR+CD28+CD8+ and HLA-DR+CD38+CD8+ subsets which were higher in TCR-TMART-1 than in Tnull.