BCG-induced formation of neutrophil extracellular traps play an important role in bladder cancer treatment

Bacillus Calmette-Guerin (BCG) is one of the most effective treatments for bladder cancer. Little attention has been paid to the possible role of neutrophils in BCG immunotherapy. In this study, we examined neutrophil extracellular traps (NETS) formation induced by BCG stimulation, and found that BCG-induced NETS exerted cytotoxicity, induced apoptosis and cell-cycle arrest, and inhibited migration in bladder tumor cells. BCG-activated tumor cells but not non-activated ones elicited NETS formation, in which IL-8 and TNF-alpha from activated tumor cells both took effect. Moreover, NETS activated peripheral blood mononuclear cells (PBMCs) exhibited a higher expression of CD4 and Th1 cytokines. Additionally, the role of NETS in vivo contributed to the recruitment of T cells and monocytes-macrophages and tissue damage, thus preventing tumor growth. NETS proteins mainly caused these effects on tumor and cellular immunity. In conclusion, we demonstrated a novel immunoregulatory role for NETS in the early stages of BCG immunotherapy.