Deciphering the role of RGS1-overexpressing CD8+T cells in immune evasion of bone metastatic cancer in the urinary system via single-cell sequencing analysis.

The bone is the most common metastatic organ for various urinary system tumors. The immunosuppressive microenvironment of bone metastatic lesions leads to poor patient prognosis, yet its regulatory mechanism remains unclear, necessitating the exploration of novel immune targets. Although the G protein signaling regulator RGS1 is associated with tumor progression and immune cell infiltration, its mechanism of action in the immune microenvironment of bone metastatic carcinoma has not been elucidated. This study aims to clarify its regulatory role in the immune microenvironment of tumor bone metastasis and the function of CD8+T cells. Single-cell RNA sequencing data were collected from bone metastatic lesions of 8 patients with renal cell carcinoma(RCC) and 9 patients with prostate cancer(PCA). A comprehensive analysis yielded 215,864 cells, which were annotated into 20 subsets. Results showed that CD8+T cells and other cell types were enriched in bone metastatic carcinoma tissues. RGS1 was highly expressed in these CD8+T cells, and CD8+T cells with high RGS1 expression exhibited an exhausted phenotype. Moreover, we established a mouse model of PCA bone metastasis and found that overexpression of RGS1 in CD8+T cells led to down-regulation of functional molecules, up-regulation of exhaustion markers, and a reduced antitumor capability. In summary, this study demonstrates that RGS1 is strongly associated with the functional and exhaustion profiles of CD8+T cells in both RCC and PCA bone metastases, offering a novel target and strategy for immunotherapy of PCA bone metastasis.