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.