Abstract
Platinum-based chemotherapy combined with immunotherapy provides durable disease control in advanced urothelial cancer. However, cisplatin and carboplatin differently impact the tumor immune microenvironment, affecting chemo-immunotherapy response. Here, we evaluate immune cell populations and ecosystems associated with overall survival in patients treated with platinum-based chemotherapy. Our transcriptomic analysis of pretreatment tumor samples from three cohorts (189 patients) of advanced urothelial cancer showed that lymphoid cell infiltration was significantly associated with prolonged overall survival. In cisplatin-treated patients, high memory B cell infiltration provided a significant overall survival improvement, but no such association was found in carboplatin-treated patients. Additionally, gene expression signatures implicated in B cell memory lineage and associated cytokines were associated with better overall survival in independent cancer patient cohorts. Our findings highlight memory B cell infiltration as a potential prognostic biomarker in urothelial cancer and emphasize the role of the tumor immune microenvironment in chemotherapy response.