Neutrophils in Cancer: Two Sides of the Same Coin

Figure 4

Antitumor activity of neutrophils. Neutrophils produce reactive oxygen species (ROS) and hypochlorous acid (HOCl) that can directly damage and destroy tumor cells. By direct contact or by release of TRAIL, neutrophils can also induce apoptosis of certain tumor cells. The most effective antitumor mechanism is antibody-dependent cell-mediated cytotoxicity (ADCC). Antibody molecules (green) that bind to tumor antigens are recognized by Fc receptors (orange circles) on neutrophils. This binding activates a cytotoxic response against the tumor cell. Neutrophils can be activated to display a stronger antitumor phenotype with granulocyte colony-stimulating factor (G-CSF), transforming growth factor-α (TNF-α), or by blocking (red cross) transforming growth factor-β (TGF-β). Also, the blockage of IL-8, with specific monoclonal antibodies (such as mAb ABX-IL8), can prevent new neutrophil infiltration into growing tumors. Inflammatory neutrophils can also activate cytotoxic (CD8) T cells. All these mechanisms result in smaller tumors. Blue arrows denote molecules secreted by cells. Green arrows denote the action of molecules on cells.