Single-Cell Transcriptome Analysis Reveals RGS1 as a New Marker and Promoting Factor for T-Cell Exhaustion in Multiple Cancers

Abstract

T-cell exhaustion is one of the main reasons of tumor immune escape. Using single-cell transcriptome data of CD8+ T cells in multiple cancers, we identified different cell types, in which Pre_exhaust and exhausted T cells participated in negative regulation of immune system process. By analyzing the coexpression network patterns and differentially expressed genes of Pre_exhaust, exhausted, and effector T cells, we identified 35 genes related to T-cell exhaustion, whose high GSVA scores were associated with significantly poor prognosis in various cancers. In the differentially expressed genes, <i>RGS1</i> showed the greatest fold change in Pre_exhaust and exhausted cells of three cancers compared with effector T cells, and high expression of <i>RGS1</i> was also associated with poor prognosis in various cancers. Additionally, RGS1 protein was upregulated significantly in tumor tissues in the immunohistochemistry verification. Furthermore, <i>RGS1</i> displayed positive correlation with the 35 genes, especially highly correlated with <i>PDCD1</i>, <i>CTLA4</i>, <i>HAVCR2</i>, and <i>TNFRSF9</i> in CD8+ T cells and cancer tissues, indicating the important roles of <i>RGS1</i> in CD8+ T-cell exhaustion. Considering the GTP-hydrolysis activity of <i>RGS1</i> and significantly high mRNA and protein expression in cancer tissues, we speculated that <i>RGS1</i> potentially mediate the T-cell retention to lead to the persistent antigen stimulation, resulting in T-cell exhaustion. In conclusion, our findings suggest that RGS1 is a new marker and promoting factor for CD8+ T-cell exhaustion and provide theoretical basis for research and immunotherapy of exhausted cells.