Turning Neutrophils into guardians: Targeting neutrophil STAT3 signaling impairs tumor growth via the modulation of their anti-tumor bias

Stat3 signaling pathway play a crucial role in pro-tumoral polarization of neutrophils. In this study, we aim to investigate the role of neutrophil-specific STAT3 deficiency (NStat3-/-) on the tumor development in head and neck cancer (HNC).We found that, NStat3-/- mice show significantly impaired tumor growth as compared to WT counterparts. TANs of such mice show distinct anti-tumoral phenotype: with shortened survival, low CD62L expression and elevated expression of molecules involved in activation of adaptive immune. Neutrophils from tumor-draining lymph nodes (TDLNs) significantly downregulate PD-L1 expression and support proliferation of CD8+T-cells. Stat3 signaling is an important driver of pro-tumoral activity of neutrophils. Here, we show that neutrophil-specific deficiency in Stat3 not only supports their anti-tumor activity, but also significantly impairs tumor development and growth, once again demonstrating the essential role of neutrophils in the regulation of tumorigenesis and suggesting them as powerful targets in cancer immunotherapy.

Funding information DFG

Publication History

Article published online:
19 April 2024