Deciphering the influence of urinary microbiota on FoxP3+ regulatory T cell infiltration and prognosis in Chinese patients with non-muscle-invasive bladder cancer.

Abstract

Despite increasing evidence that dysbiosis of urinary microbiota is closely correlated with bladder cancer, the influence of the urinary microbiota on immune evasion and tumor growth in bladder cancer is unknown. This study investigated whether the urinary microbiota influences intratumoral infiltration of FoxP3+ regulatory T cells, expression of Ki-67 and clinical prognosis in non-muscle-invasive bladder cancer. Forty male patients, including 12 and 28 with or without recurrence, respectively, were retrospectively enrolled. Midstream urine samples were preoperatively collected. Urinary microbiota composition was analyzed by 16s rDNA sequencing. Alpha and beta diversities were measured. LEfSe analysis was employed to identify specific bacteria associated with recurrence. Intratumoral infiltration of FoxP3+ regulatory T cells and Ki-67 expression were evaluated by immunohistochemistry. Patients with recurrence had higher α-diversity compared to those without (Shannon Index, P = 0.0007, Simpson Index, P = 0.0004). Distinct beta diversity was observed between recurrence and non-recurrence groups (weighted Unifrac P = 0.02; unweighted Unifrac P = 0.001). LEfSe analysis showed that the recurrence group displayed marked enrichment of Pseudomonas, Staphylococcus, Corynebacterium, and Acinetobacter genera. Patients with higher alpha diversity had elevated Ki-67 expression than those with lower alpha diversity (P = 0.0194), although microbial diversity was unassociated with infiltration of FoxP3+ regulatory T cells (P = 0.1653). Patients with lower urinary microbial diversity had prolonged recurrence-free survival compared to those with higher diversity. Perturbation of urinary microbiota may induce immune evasion and tumor growth, eventually contributing to unfavorable outcomes. Additional study is warranted to confirm a causal role of urinary microbiota in modulating antitumor immune response and survival in bladder cancer.