Figure 3.

Neutrophils can promote or inhibit the anti-tumor response of lymphoid cells. (A) Immunosuppression can be mediated by neutrophils via the production of reactive oxygen species (ROS), reactive nitrogen intermediate (RNI) and arginase-1 (Arg-1) or through fatty acid transporter protein 2 (FATP2)-dependent production of prostaglandin E2 (PGE2). (B) Neutrophils can indirectly affect the cytotoxic activity of NK cells and CD8⁺ T cells by releasing neutrophil extracellular traps (NETs) that shield cancer cells. (C) Neutrophils express immune checkpoints such as programmed cell death 1 ligand 1 (PD-L1) or the V-domain immunoglobulin suppressor of T-cell activation (VISTA) that, by binding to their ligands PD-1 and P-selectin glycoprotein ligand-1 (PSG-L1), cause T cell and NK cell dysfunction. (D) Neutrophils can acquire antigen presenting cell-like (APC-like) features under the influence of GM-CSF or interferon (IFN)-γ or upon phagocytosis of antibody-antigen complexes via Fc gamma receptors (FcγRs). Similarly, neutrophils enhance TCR signaling in CD8⁺ T cells through the interaction between CD54/intercellular adhesion molecule 1 (ICAM-1) expressed on neutrophils and CD11a expressed on T cells. (E) Tool like receptor (TLR)-stimulated neutrophils can attract and activate NK cells which, in turn, trigger the maturation of dendritic cells resulting in T cell proliferation and IFN-γ production.