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-α 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.
Clinical immunology (Orlando, Fla.). 2019 Feb 13 [Epub ahead of print]
Kangkang Liu, Erlin Sun, Mingde Lei, Limin Li, Jingda Gao, Xuewu Nian, Lining Wang
Tianjin Institute of Urology, Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, PR China., Tianjin Institute of Urology, Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, PR China. Electronic address: ., Department of Urology, The 4th People's Hospital of Hengshui, Hengshui 053000, PR China., Department of Urology, Children's Hospital of Hebei Province, Shijiazhuang 050031, PR China., Department of Urology, Tianjin Nankai Hospital, Tianjin 300100, PR China.