Fig. 2

Neutrophil reprogramming in the tumor microenvironment. During cancer progression, cytokines, particularly TGF-β and G-CSF, secreted from tumors (and probably stromal cells) stimulate transition of neutrophils from an anti-tumor to a pro-tumor phenotype. Conversely, pro-tumor neutrophils can be reprogrammed by cytokines (i.e., IFN-β), released from the tumor microenvironment such as dendritic cells and/or macrophages to become anti-tumorigenic. Basically, the anti-tumor neutrophils are developmentally more mature with a more segmented nucleus than the pro-tumor cells, which have a more ring-like structure of the nucleus. The anti-tumor neutrophils express higher levels of cytokines such as CCL3, TNF-α, and ICAM1. They also have higher levels of ROS such as H₂O₂ and O₂‧, and RNS such as NO. In contrast, the pro-tumor neutrophils have higher levels of Arg1, CD206, Ym1, IL-6, CCL17, CXCR4, NE, MMP9, VEGF, and PROK2