Viral infections and immune modulation in bladder cancer: implications for immunotherapy

Abstract

This review explores the intricate relationship between viral infections and Bacillus Calmette-Guerin (BCG) efficacy, emphasizing immune modulation mechanisms that may influence treatment outcomes. Since its introduction in 1976, intravesical BCG has been a cornerstone in managing non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumors (TURBT). Despite its success, variability in response rates suggests that host immune status, influenced by persistent infections, immunosenescence, and antigenic overload, may play a crucial role in therapeutic effectiveness. Chronic viral infections can modulate T cell responses, leading to immune exhaustion and impaired antitumor immunity. This review discusses the interplay between viral antigenic load, immune dysfunction, and tumor microenvironment remodeling, highlighting their potential impact on immunotherapies. By integrating insights from virome analysis, immune profiling, and tumor characterization, this review proposes personalized strategies to enhance immunotherapy efficacy. A deeper understanding of viral-induced immune dysregulation may improve prognostic assessment, optimize treatment protocols, and reduce healthcare costs associated with bladder cancer. Future research should focus on targeted interventions to mitigate the immunosuppressive effects of chronic infections, ultimately improving patient outcomes in NMIBC management.

Keywords: Virome; exhaustion; immune response; senescence; urothelial carcinoma.

Figure 1

Modulation/efficiency of the immune response: environmental factors, aging, and chronic exposure mechanisms. The upper part: Created in BioRender. Bitencourt Pascoal, L. (2025) https://biorender.com/8vidydm; the lower part: Created in BioRender. Bitencourt Pascoal, L. (2025) https://biorender.com/qhkm6ia