Decoding the Immune Microenvironment of Clear Cell Renal Cell Carcinoma by Single-Cell Profiling to Aid Immunotherapy

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, and it is the major cause of kidney cancer death. Understanding tumor immune microenvironments (TMEs) is critical in cancer immunotherapies. Here, we studied the immune characterization at single-cell resolution by integrating public data of ccRCC across different tissue types, and comparing the transcriptome features and tumor TME differences in tumors, normal adjacent tissue, and peripheral blood. A total of 16 different types of cell components of ccRCC were identified. We revealed that there is an overall increase in T-cell and myeloid populations in tumor-infiltrated immune cells compared to normal renal tissue, and the B-cell population in the tumor showed a sharp decrease, which indicates that the cells in tumor tissue undergo strong immune stress. In addition, the cell-cell communication analysis revealed specific or conserved signals in different tissue types, which may aid to uncover the distinct immune response. By combining and analyzing publicly available ccRCC bulk RNA-seq datasets, 10 genes were identified as marker genes in specific cell types, which were significantly associated with poor prognosis. Of note, UBE2C, which may be a good indicator of tumor proliferation, is positively associated with reductions in overall survival and highly associated with tumor grade. Our integrated analysis provides single-cell transcriptomic profiling of ccRCC and their TME, and it unmasked new correlations between gene expression, survival outcomes, and immune cell-type components, enabling us to dissect the dynamic variables in the tumor development process. This resource provides deeper insight into the transcriptome features and immune response of ccRCC and will be helpful in kidney cancer immunotherapy.