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Gene Expression in Human Polymorphonuclear Neutrophils (PMNs) Stimulated by Bacillus Calmette-Guérin (BCG)
Kangkang Liu1, Erlin Sun2, Lining Wang1
1Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, No. 23, PingJiang Road, Hexi District, Tianjin, 300211, People's Republic of China.
Abstract:
Neutrophils are the most abundant leukocytes in the blood. Moreover, neutrophils form the first line of host immune defense against bacterial and fungal invasion, and also play an important part in inflammatory and immune system responses. Intravesical bacillus Calmette-Guérin (BCG) has been shown to reduce and delay tumor progression to muscle-invasive disease after transurethral resection of bladder tumors (TRUBTs). Following intravesical BCG, neutrophils gather around tissues infected by BCG in the early stage of inflammatory and immune responses. In our previous study, we reported that BCG induced the formation of neutrophil extracellular traps (NETs), which play an important role in tumor treatment. Therefore, in the present study, we analyzed the gene expression profile of neutrophils stimulated by BCG through high-throughput arrays, which helped us determine the potential roles of neutrophils in BCG immunotherapy. The results showed that the expression of neutrophil genes led to changes in the early stage of BCG stimulation. The changed genes were involved in many functions of neutrophils such as mobility, proliferation, and secretion of cytokines, chemokines, and adhesion molecules. These changes in neutrophil biological functions may play an essential role in BCG induction of inflammatory and immune responses, and in anti-tumor processes.
Insights
Bacillus Calmette-Guérin (BCG) immunotherapy alters neutrophil gene expression, impacting immune responses and anti-tumor activity. Understanding these neutrophil changes is key to optimizing BCG treatment for bladder cancer.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Neutrophils are crucial immune cells, acting as the first line of defense against pathogens and influencing inflammation.
- Intravesical bacillus Calmette-Guérin (BCG) is a standard treatment for non-muscle-invasive bladder cancer, delaying progression.
- Previous research indicated BCG induces neutrophil extracellular traps (NETs), vital for anti-tumor effects.
Purpose of the Study:
- To investigate the gene expression profile of neutrophils stimulated by BCG.
- To elucidate the functional roles of neutrophils in BCG immunotherapy.
- To understand the early-stage molecular mechanisms of BCG's anti-tumor effects mediated by neutrophils.
Main Methods:
- Analysis of neutrophil gene expression using high-throughput arrays after BCG stimulation.
- Comparative analysis of gene expression profiles to identify significant changes.
Main Results:
- BCG stimulation significantly altered neutrophil gene expression in the early stages.
- Affected genes were associated with neutrophil functions including mobility, proliferation, and secretion of cytokines, chemokines, and adhesion molecules.
- These molecular changes highlight neutrophils' multifaceted roles in BCG-induced inflammation and anti-tumor responses.
Conclusions:
- Neutrophil gene expression modulation is an early event in BCG immunotherapy.
- Altered neutrophil functions contribute to the inflammatory and anti-tumor efficacy of BCG.
- Targeting neutrophil responses could enhance BCG immunotherapy outcomes for bladder cancer.
