Prognostic significance of CD4-positive regulatory T cells in tumor draining lymph nodes from patients with bladder cancer

INTRODUCTION AND METHODS: To clarify the role of CD4(+) regulatory T cells in bladder cancer, we investigated the frequency of these cells in tumor draining lymph nodes of 50 patients with bladder cancer who underwent radical cystectomy using flow cytometry method. We also assessed their association with prognosis and survival. RESULTS: On average, 30.13 ± 2.17% of lymphocytes in draining lymph nodes from patients with bladder cancer were positive for both CD4 and FOXP3 molecules. Analyses also showed that 9.92 ± 0.8% of CD4(+) lymphocytes had a regulatory phenotype (CD4(+)CD25(+)FOXP3(+)CD127(low/neg)). The frequency of total CD4(+)FOXP3(+) lymphocytes as well as regulatory T cells was significantly greater in patients with at least one tumor-involved lymph node compared to those with tumor-free nodes (P = 0.026 and P = 0.036, respectively). Mean FOXP3 expression in CD4(+) lymphocytes was greater in patients with stage IV compared with those in stage III (P = 0.046). No other significant associations were found between the frequency of regulatory T cells and other clinicopathological characteristics or patient survival. CONCLUSIONS: The increased frequency of regulatory T cells in patients with involved lymph nodes suggests that these cells may negatively regulate antitumor immune responses in draining lymph nodes. Our findings may have implications for immunotherapy-based treatments for bladder cancer.