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, RGS1 showed the greatest fold change in Pre_exhaust and exhausted cells of three cancers compared with effector T cells, and high expression of RGS1 was also associated with poor prognosis in various cancers. Additionally, RGS1 protein was upregulated significantly in tumor tissues in the immunohistochemistry verification. Furthermore, RGS1 displayed positive correlation with the 35 genes, especially highly correlated with PDCD1, CTLA4, HAVCR2, and TNFRSF9 in CD8+ T cells and cancer tissues, indicating the important roles of RGS1 in CD8+ T-cell exhaustion. Considering the GTP-hydrolysis activity of RGS1 and significantly high mRNA and protein expression in cancer tissues, we speculated that RGS1 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.

Single-cell gene expression analysis of cryopreserved equine bronchoalveolar cells

“…Interestingly, the top differentially expressed gene was KLRF1 , a cytotoxicity regulator whose expression is associated with exhaustion of human memory CD4 + T cells ( 37 ). RGS1 , a marker of exhaustion in CD8 + T cells ( 38 ), was also upregulated in this cluster.…”

RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation

“…RGS1 promotes melanoma progression by regulating Gαs-mediated inactivation of AKT and ERK, and is a novel therapeutic target and prognostic marker for melanomas [ 13 , 14 ]. In addition, RGS1 is highly expressed in multiple malignancies and predicts poor prognosis in cancers [ 15 ].…”

GITR and TIGIT immunotherapy provokes divergent multi-cellular responses in the tumor microenvironment of gastrointestinal cancers

“…GC-1-2 CD8 T cells had significantly higher expression of GZMK ( Fig. 6G ) associated with effector memory CD8 cells (2) and RGS1 associated with pre-exhausted and exhausted CD8 T cells (39). The reduced responsive cells also had upregulated TXNIP , which has been demonstrated to reduce effector functions in CD8 T cells in viral infection (40).…”