Neutrophils and neutrophil extracellular traps: double-edged swords in cancer pathophysiology and therapy resistance

Among white blood cells (WBCs), neutrophils are the most abundant and multifunctional immune cells in the blood, which are also involved in diverse physiological and pathological processes, particularly affecting the deterioration of the tumor. Neutrophil extracellular traps (NETs), composed of chromatin DNA studded with granule proteins, play a crucial role in reactive sterile inflammation. Recently, neutrophils have garnered focus in cancer research due to their participation in cancer initiation, proliferation and metastasis. As important players in the tumor microenvironment (TME), tumor-associated neutrophils (TANs) are viewed as “a double-edged sword” in cancer pathophysiology.In this review, we introduce the NETs formation and associated signaling pathways. Meanwhile, recent studies on the mechanisms through by which neutrophils could promote tumors development will be described. Additionally, we outline the complex complicated molecular mechanisms underlying cancer therapy resistances and associated preface tumor treatment. Finally, we highlight latest advances in NETs-targeting treatment strategies designed to improve the efficacy of cancer therapies. The oncogenic effect of neutrophils is included. The formation of NETs promotes tumor initiation, metastasis and the therapy resistance of cancer conventional drugs. Almost all signaling pathways associated with NETs have been summarized in tumor progression and metastasis. We comprehensively discussed the important role of neutrophils in the development of cancer and proposed the strategy of reducing NETs formation in the future treatment of cancer.