Tumor-associated neutrophils (TANs) are immune cells with strong functional plasticity in the tumor microenvironment (TME). Their infiltration, activation, polarization balance, and formation of neutrophil extracellular traps (NETs) profoundly affect tumor occurrence, development, and immune responses. Polarization imbalance of TANs and excessive formation of NETs are key mechanisms underlying tumor immune evasion. The core pathogenesis of “deficiency-stasis-toxin” in traditional Chinese medicine (TCM) is closely related to the abnormal function of TANs: deficiency of healthy qi is the fundamental prerequisite for the abnormal function of TANs; intertwining of phlegm and stasis provides a pathological basis for the pro-tumor microenvironment of TANs; and internal accumulation of heat-toxin drives abnormal activation of TANs and amplification of inflammation. With the advantages of multi-target and multi-pathway effects, TCM regulates signaling pathways such as C-X-C motif chemokine ligand 1 (CXCL1)/C-X-C motif chemokine receptor 2 (CXCR2), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), nuclear factor-κB (NF-κB), signal transducer and activator of transcription 3 (STAT3) through therapeutic methods including reinforcing healthy qi and eliminating pathogens; resolving phlegm and removing stasis; clearing heat and resolving toxin. These methods can inhibit the abnormal recruitment and activation of TANs, regulate the N1/N2 polarization balance, and reduce NETs production, thereby improving the immunosuppressive state of TME and blocking tumor progression. From the perspective of integrated TCM and Western medical theories, this article systematically explains the tumor regulatory mechanism of TANs and its intrinsic correlation with the core pathogenesis of “deficiency-stasis-toxin” in TCM. It also analyzes the functional mechanism of TCM in regulating TANs based on existing research, which not only lays a theoretical foundation for revealing the scientific connotation of TCM in anti-tumor therapy but also provides core theoretical support for constructing a new integrated TCM and Western medicine strategy for TANs-targeted antitumor therapy.

deficiency-stasis-toxin  /  traditional Chinese medicine  /  tumor-associated neutrophils  /  tumor microenvironment  /  neutrophil polarization  /  neutrophil extracellular traps