Specific subsets of urothelial bladder carcinoma infiltrating T cells associated with poor prognosis

Comprehensive investigation of tumor-infiltrating lymphocytes in cancer is crucial to explore the effective immunotherapies, but the composition of infiltrating T cells in urothelial bladder carcinoma (UBC) remains elusive. Here, single-cell RNA sequencing (scRNA-seq) were performed on total 30,905 T cells derived from peripheral blood, adjacent normal and tumor tissues from two UBC patients. We identified 18 distinct T cell subsets based on molecular profiles and functional properties. Specifically, exhausted T (T Ex ) cells, exhausted NKT (NKT Ex ) cells, Ki67 + T cells and B cell-like T (B-T) cells were exclusively enriched in UBC. Additionally, the gene signatures of T Ex , NKT Ex , Ki67 + T and B-T cells were significantly associated with poor survival in patients with BC and various tumor types. Finally, IKZF3 and TRGC2 are the potential biomarkers of T Ex cells. Overall, our study demonstrated an exhausted context of T cells in UBC, which layed a theoretical foundation for the development of effective tumor immunotherapies.