Fig. 1

Intercellular communication between NETs and tumor cells or immune cells. a NET-DNA served as a chemotactic factor, which was sensor by cell-surface receptor CCDC25 on the metastatic tumor cell, and subsequently activated the downstream ILK–β-Parvin signaling to accelerate the metastasis. b NETs functioning as a substrate for the integrins expressed on the tumor cell, could enhance the cell adhesion ability and sequester the CTC. c NET-remodeled laminin-111 contributed to tumor proliferation by activating the integrin a3β1 signaling of the dormant cancer cell. d NET clearance refers to the process by which macrophage phagocytoses the NET. NET clearance is often impaired in cases of abnormal immunity. Specific molecules could enhance the ability of NET clearance through the cAMP/PKA/AMPK axis. e The impact of NETs on the immunomodulatory function may be due in part to the phenomenon of NETs-shielding tumor cells, reducing the direct contact between effector cytotoxic lymphocytes and tumor cells. f NET-primed naïve CD4⁺ T cell was more inclined to the differential of Treg cell through increasing the mitochondrial OCR and OXPHOS. Genes essential for Treg differentiation and activity were up-regulated. Meanwhile, Teff programming genes were significantly down-regulated. g Activated platelets bind to the receptor P-selective (P-sel) glycoprotein ligand-1 (PSGL-1) on the surface of the neutrophil via P-selective protein and promote the production of NETs. And NETs such as the DNA backbone and adherent thrombosis-related enzymes can activate platelets in turn