Figure 4.

Neutrophils in TME or TIME and their immunometabolic reprogramming. The systemic neutrophil number increases in tumor patients. This increase is due to the increased neutrophil generation in the bone marrow (BM), causing increased infiltration in the TME or TIME. Although only mature neutrophils leave the BM, TIME contains both immature and mature neutrophils. Therefore, different chemokines and cytokines released from TME or TIME cells send the signals to BM for neutrophil chemotaxis. Additionally, ATP released from tumor-associated neutrophils (TANs) acts in an autocrine manner via P2Y purinergic receptors to further support their chemotaxis in TME or TIME. TANs show an increased rate of OXPHOS and glycolysis along with an elevated PPP. The ROS released from TANs induced apoptotic cell death among infiltrated antitumor T cells, causing immunosuppression. Hypoxia in TME or TIME causes NETosis that further supports tumor metastasis. See the text for details.