Fig. 6.

The Yin and Yang profiles of neutrophils in the progression of cancer. β-glucan and BCG stimulate neutrophils to develop antitumor innate immune memory in the bone marrow. Antitumor neutrophils (N1) induce tumor apoptosis by activating T cells and NK cells and releasing cytokines. However, tumor-derived factors and microbes can influence neutrophils to adopt a protumorigenic phenotype (N2). N2 neutrophils contribute to an immunosuppressive microenvironment by recruiting M2-type macrophages and Tregs. They also secrete mediators that directly promote tumor progression. IFN and TGF-β drive the formation of N1 and N2 neutrophil phenotypes, respectively. Moreover, neutrophil polarization varies based on tumor characteristics and patient status. Discontinuation of surgery, chemotherapy, and radiotherapy can lead to neutrophil-induced tumor recurrence. Adjuvant therapy using immunoagonists (e.g., β-glucan, BCG vaccine) and immunosuppressants (e.g., PD-L1, STAT3 inhibitors) enhances the antitumor effect of neutrophils. Poor patient habits, endogenous factors, and tumor metabolic reprogramming influence the tumor-promoting effect of neutrophils