BCG prophylaxis in bladder cancer produces activation of recruited neutrophils

Bacillus Calmette-Guerin (BCG) is used to treat high risk superficial bladder cancer, but its anti-tumor effect remains incompletely defined. Recently a role for polymophonuclear (PMN) neutrophils has been suggested. To investigate the role of granulocytes, we monitored the activation state of these cells in the urine of BCG-treated patients.

Ten patients with stage T1, grade 3 (T1G3) transitional cell carcinoma received an 8 week course of BCG after undergoing transurethral resection of the bladder. Cytological and enzymatic analyses of urine samples collected before and 2 hours after the physiological expulsion of BCG were performed. The activation state of urine granulocytes and the presence of activating factors within the urine samples were monitored.

BCG immunotherapy stimulated, through soluble factors, the activation of PMN neutrophils, which transmigrated into the bladder, and the degree of activation of the PMN neutrophils was related directly to the number of epithelial cells detached from the urothelial layer.

This study suggests that PMN neutrophils can participate in reducing the recurrence of bladder cancer by promoting urothelial cell turnover proportionally to their degree of activation. Our results provide further evidence to support the role of PMN neutrophils in BCG immunotherapy.