N1 and N2 Neutrophils in Breast Cancer: Mechanisms, Clinical Relevance, and Therapeutic Potential

Neutrophils are key components of the immune system and play a significant role in the tumour microenvironment (TME) of breast cancer. These cells can undergo polarization into two distinct phenotypes: N1 and N2 neutrophils. N1 neutrophils are typically associated with antitumor immunity, characterized by the production of pro-inflammatory cytokines and reactive oxygen species (ROS), which help inhibit tumour growth and metastasis. On the other hand, N2 neutrophils contribute to tumour progression by secreting immunosuppressive cytokines, promoting angiogenesis, and enhancing metastatic spread. The balance between these two phenotypes can have significant implications for cancer progression and treatment outcomes in breast cancer patients. The polarization of neutrophils is regulated by a complex network of cytokines, growth factors, and signalling pathways in the TME. Factors such as IL-12, IFN-γ, and GM-CSF promote N1 polarization, while IL-10, TGF-β, and VEGF are key drivers of N2 polarization. These pathways influence neutrophil recruitment, activation, and survival within the TME. Strategies targeting neutrophil polarization could offer new opportunities for breast cancer treatment, particularly for patients with aggressive or metastatic disease.