The Interplay of Microbiome and Immunity in Urothelial Cancers

Urothelial cancer, encompassing malignancies of the bladder and upper urinary tract, remains a significant clinical challenge due to high recurrence rates and heterogeneous responses to therapy. In recent years, the concept of the urinary tract as a sterile environment has been overturned, revealing a complex and dynamic microbiome that may critically influence tumor initiation, progression, and therapeutic outcomes. This special issue focuses on the emerging evidence describing the bidirectional crosstalk between the microbiome and host immunity in urothelial cancer. Microbial communities residing in the urinary tract and gut can modulate local and systemic immune responses through multiple mechanisms, including the production of metabolites such as short-chain fatty acids, modulation of antigen presentation, and regulation of inflammatory pathways. These interactions can shape the tumor microenvironment, influencing immune cell infiltration, polarization, and function, ultimately affecting tumor growth and response to treatments such as Bacillus Calmette–Guérin (BCG) immunotherapy and immune checkpoint inhibitors. Contributions to this issue will explore the role of microbial dysbiosis in urothelial carcinogenesis, the impact of host–microbiome interactions on immune surveillance and immune evasion, and the potential of microbiome-based biomarkers for patient stratification. Additionally, innovative therapeutic strategies aimed at modulating the microbiome—through probiotics, antibiotics, diet, or fecal microbiota transplantation—will be examined as adjuncts to conventional and immunotherapeutic approaches. By integrating microbiology, immunology, and oncology, this special issue aims to provide a comprehensive overview of a rapidly evolving field and to highlight novel translational opportunities for improving diagnosis, prognosis, and personalized treatment in urothelial cancer.