Fig. 2: Neutrophil apoptosis and efferocytosis in cancer.

Tissue-infiltrating neutrophils that are attracted by tumor-derived signals are exposed to a variety of survival factors originating from tumor cells, stroma, hypoxia, or dying cells. They may propagate the inflammatory tumor microenvironment by recruiting and activating further leukocytes, such as cytotoxic T-cells. Tumor-associated neutrophils have the potential to reverse migrate into circulation, thereby facilitating metastasis of attached tumor cells. However, the majority of them is proposed to undergo local apoptosis and subsequent efferocytosis by macrophages, which drives an anti-inflammatory M2-like polarization, tumor proliferation, and vascularization. Conversely, neutrophils may remove apoptotic tumor cells by efferocytosis and thereby promote tissue remodeling and cancer growth.