Decoding the metabolic-immune axis for novel therapeutics in bladder cancer

Bladder cancer is a prevalent malignancy of the urinary system. Urothelial carcinoma is the predominant type, accounting for more than 90% of cases. The remaining histologic types include squamous cell carcinoma (approximately 2%-7%) and adenocarcinoma (approximately 1%-2%). Within urothelial carcinoma, the papillary subtype is responsible for approximately roughly 70% of cases, and it is often linked to high-frequency gene mutations (e.g., FGFR3 and TP53) and epigenetic alterations, such as DNA hypermethylation-mediated silencing of genes, including RASSF1A and CDH1, and disruptions in histone modification attributable to histone deacetylase overexpression. Platinum-based chemotherapy remains the standard first-line treatment for advanced disease. However, recent research efforts have concentrated on targeted therapy, immunotherapy, metabolic reprogramming, and novel biotechnological applications. In particular, the dynamic interplay between tumor cell metabolic reprogramming and the immune suppressive tumor microenvironment, collectively termed the "metabolic-immune axis", constitutes a major challenge underlying drug resistance. This review summarizes how this axis, through mechanisms such as enhanced glycolysis and abnormal amino acid/lipid metabolism, influences bladder cancer progression and treatment responsiveness, thereby establishing a theoretical framework for future research directions.