Microbiome and immunotherapy in bladder cancer: The missing link

Bladder cancer remains a significant global health concern, with immunotherapies such as Bacillus Calmette-Guérin (BCG) and immune checkpoint inhibitors (ICIs) playing pivotal roles in treatment. Emerging evidence suggests that the microbiome, encompassing both gut and urinary tract microorganisms, may influence the efficacy and outcomes of these immunotherapies.

This review aims to explore the intricate relationship between the microbiome and immunotherapy in bladder cancer, highlighting current research findings, potential mechanisms, and future therapeutic implications.

A comprehensive literature search was conducted across databases including PubMed and Scopus, focusing on studies published up to March 2025. Keywords utilized encompassed "bladder cancer", "microbiome", "immunotherapy", "BCG therapy", and "immune checkpoint inhibitors".

The analysis indicates that specific microbial compositions are associated with varied responses to bladder cancer immunotherapies. Notably, certain gut microbiota profiles correlate with enhanced ICI efficacy, while alterations in the urinary microbiome may impact BCG treatment outcomes. Potential mechanisms involve microbial modulation of systemic and local immune responses, influencing tumor microenvironments and therapeutic effectiveness.

Understanding the microbiome's role in bladder cancer immunotherapy presents a promising avenue for optimizing treatment strategies. Further research is imperative to elucidate these relationships and translate findings into clinical practice, potentially leading to microbiome-targeted interventions to improve patient outcomes.