Tumor B-cell infiltration in platinum-treated advanced muscle-invasive urothelial carcinoma

Platinum chemotherapy is a standard therapeutic choice for advanced urothelial cancer, but biomarkers demonstrating its benefits are limited. We tested whether the tumor microenvironment, particularly B-cell infiltration, could predict overall survival after platinum chemotherapy. Pretreatment tumors from 189 patients in three cohorts treated with cisplatin- or carboplatin-based regimens underwent bulk transcriptome profiling. Immune cell infiltration and multicellular communities were inferred from gene expression and associated with overall survival using cohort-specific multivariable models and meta-analysis. Higher lymphocyte infiltration was associated with longer overall survival (hazard ratio 0.34, 95% confidence interval 0.16-0.72), driven by B cells and memory B cells (hazard ratio 0.19, 95% confidence interval 0.05-0.75). These associations were confined to cisplatin-treated patients and were strongest in tumors with a pro-inflammatory B-cell-rich community and concordant B-cell gene expression signatures. In contrast, higher myeloid infiltration was associated with shorter overall survival. Pretreatment B-cell enrichment in the tumor microenvironment identified a subset associated with improved overall survival among patients receiving platinum chemotherapy, particularly cisplatin, supporting B-cell-focused biomarker development and spatial characterization of tertiary lymphoid structures in urothelial cancer.