Fig. 3.

Neutrophils regulate immune cells to drive antitumor immune responses. When exposed to IFN-γ and GM-CSF, immature neutrophils can differentiate into hybrid neutrophils with antigen-presenting cell (APC) characteristics. Thereafter, dendritic cells and APC-like neutrophils can pick up tumor antigens and migrate to lymph nodes (LNs). In LNs, these antigen-presenting cells cross-present tumor antigens to T cells using MHC molecules and costimulatory ligands (CD80/CD86 on dendritic cells and APC-like neutrophils and CD28 on T cells), thereby stimulating antitumor T cell responses. Activated T cells then exit the LN and specifically target and eliminate tumor cells. Tumor cells can undergo antigenic variations, leading to the formation of tumor variants with diverse antigenic profiles. In response, activated T cells can secrete chemokines to recruit neutrophils, which contribute to the elimination of antigenically heterogeneous tumors by releasing NO. Interferons play critical roles in inducing antitumor immune responses in neutrophils. IL-12, secreted by dendritic cells and macrophages, triggers the type I activation of T cells and αβ T cells, resulting in the production of IFN-γ. Subsequently, activated neutrophils can further stimulate macrophages to release IL-12, amplifying the antitumor immune response