Fig. 4: Hierarchical clustering of gene signatures representing T cells, immune cells and stromal cells and their products distinguishes responders from non-responders to pembrolizumab.

Transcriptomic profile of 41 patients with metastatic urothelial carcinoma (mUC), clustered using ConsensusClusterPlus v1.54.0³⁸ according to gene signature scores. Transcriptomic and clinical features are listed from top to bottom as follows: response to treatment at 6 months of therapy (responder: ongoing complete or partial response, or stable disease, n = 13; non-responder: progressive disease, n = 28); tumor mutational burden (TMB) classified into high and low; APOBEC enrichment analysis showing tumors with no-, low-, medium- and high-APOBEC mutagenesis; transcriptomic subtypes of mUC³⁰; biopsy site; primary tumor location (bladder or upper tract urothelial carcinoma, UTUC); tumor purity; patients who received systemic treatment prior to start of anti-PD-1 therapy; PD-L1 combined positivity score (CPS; positive: CPS ≥ 10, negative: CPS < 10, or not available (NA)); CD274 (PD-L1) and PDCD1 (PD-1) gene expression; expression score for reported gene signatures related to T cells, immune cells (non-T cells), and stromal cells and their products; T cell-to-stroma enrichment (TSE) score; categories of the TSE score (positive, neutral or negative); T cell receptor (TCR) diversity index and clonotype sizes. Source data are provided as a Source Data file.