Decoding the role of exosomes in bladder cancer: focusing on tumor progression and immune microenvironment modulation

Bladder cancer (BCa) remains one of the most prevalent urological malignancies worldwide and is characterized by high recurrence rates and substantial therapeutic challenges in advanced disease. Exosomes, a nanoscale subtype of extracellular vesicles, have emerged as important mediators of intercellular communication within the tumor microenvironment (TME). This review summarizes the roles of exosomes in BCa progression, immune microenvironment modulation, biomarker development, drug delivery, and immunotherapy, while critically distinguishing preclinical observations from early clinical biomarker evidence. BCa-associated exosomes can promote tumor growth, metastasis, angiogenesis, metabolic reprogramming, and chemoresistance by transferring bioactive cargoes, including microRNAs, long non-coding RNAs, proteins, lipids, and metabolites. Within the tumor immune microenvironment (TIME), BCa-derived exosomes contribute to immune evasion by promoting M2 macrophage polarization, impairing dendritic-cell function, and suppressing natural killer (NK)-cell and T-cell activity. To clarify the context-dependent effects of exosomes, we propose a cargo-context-recipient framework in which exosomal function is determined by the molecular cargo, the biological and therapeutic context, and the functional state of the recipient cell. Because urine provides direct access to bladder-derived vesicles, urinary exosomes show promise as non-invasive diagnostic and prognostic biomarkers, although most studies remain limited by small cohorts and require independent validation. Exosomes also represent potential drug-delivery and immunomodulatory platforms; however, bladder cancer-specific therapeutic evidence remains largely preclinical. Clinical translation is constrained by heterogeneity in exosome isolation and quantification, limited standardization, insufficient mechanistic validation, and a paucity of BCa-specific interventional trials. A more critical, mechanism-guided, and evidence-stratified framework is therefore needed to move exosome research in BCa from descriptive cargo cataloguing toward clinically actionable biomarkers and therapeutic strategies.