Research progress in augmentation strategies for PD-1/PD-L1 inhibitors in bladder cancer: from biological determinants to clinical applications

PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have demonstrated significant clinical efficacy in the treatment of bladder cancer. However, heterogeneous patient responses continue to limit the widespread adoption and overall effectiveness of these therapies. Consequently, identifying strategies to enhance treatment response has become a primary focus of current oncological research. This review summarizes the biological determinants of immune response in bladder cancer, including sex, gut microbiota, molecular subtypes, and the tumor microenvironment (TME). Furthermore, we evaluate key predictive biomarkers for ICI response, such as PD-L1 expression, tumor mutational burden (TMB), and circulating tumor DNA (ctDNA). Synergistic combination strategies-incorporating chemotherapy, radiotherapy, targeted therapy, and nanomedicine-are also detailed to provide novel insights into bladder cancer immunotherapy. Ultimately, the systematic elucidation of immune response mechanisms combined with technological innovation will facilitate the optimization of therapeutic strategies, leading to improved clinical outcomes for patients.