NETosis: Sculpting tumor metastasis and immunotherapy

Abstract

The process of neutrophil extracellular traps (NETs) formation, called NETosis, is a peculiar death modality of neutrophils, which was first observed as an immune response against bacterial infection. However, recent work has revealed the unique biology of NETosis in facilitating tumor metastatic process. Neutrophil extracellular traps released by the tumor microenvironment (TME) shield tumor cells from cytotoxic immunity, leading to impaired tumor clearance. Besides, tumor cells tapped by NETs enable to travel through vessels and subsequently seed distant organs. Targeted ablation of NETosis has been proven to be beneficial in potentiating the efficacy of cancer immunotherapy in the metastatic settings. This review outlines the impact of NETosis at almost all stages of tumor metastasis. Furthermore, understanding the multifaceted interplay between NETosis and the TME components is crucial for supporting the rational development of highly effective combination immunotherapeutic strategies with anti-NETosis for patients with metastatic disease.