Mechanisms of microbiome-immune interactions in bladder cancer and targeted regulatory strategies

Abstract

Bladder cancer (BC), a highly prevalent malignancy of the urinary tract, imposes a considerable clinical burden because of its high recurrence rates and a substantial risk of disease progression. Accumulating evidence suggests that microbiome dysbiosis is associated with the initiation and progression of BC through potentially bidirectional interactions. Recent advances in high-throughput sequencing technologies have facilitated a more comprehensive characterization of the urinary microbiome, thereby revealing its potential involvement in the pathogenesis of BC. This review summarizes the proposed mechanisms through which microbial communities may contribute to BC carcinogenesis, including chronic inflammation, microbial metabolite production, and epigenetic regulation. We further critically evaluate the established mechanisms of Bacillus Calmette–Guérin (BCG) immunotherapy—a standard intravesical immunotherapy for patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC)—and examine the emerging application of microbiome profiling as a source of candidate noninvasive biomarkers and potential correlates or modulators of immune checkpoint inhibitor (ICI) response. Additionally, we elucidate the associations between microbiota heterogeneity and immunotherapy response, offering novel insights into microbiome-targeted therapeutic strategies for BC.