NETs in cancer

Abstract

Many aspects of neutrophil hyperactivity and its role in numerous immune responses still remain a mystery. A new neutrophil mechanism was discovered recently, i.e., the formation of neutrophil extracellular traps (NETs). These structures, composed of DNA strands and neutrophil granule proteins, are an element of the non-specific immune response and bind pathogens to prevent their spread and ensure increased local concentrations of toxic factors. Research on this phenomenon shows that tumor-associated neutrophils (TANs) also form and release NETs. Reports on the role of NETs in the course of cancer are scarce, and the opinions on the involvement of extracellular traps in the disease are divided, indicating a dual function. There is speculation about the anti-cancer properties of NETs connected with direct killing of cancer cells or stimulation of the immune system. On the other hand, the trap structures might promote migration and immune escape of cancer cells or constitute a physical barrier between cancer cells and immune-competent cells. This article summarizes our knowledge about the proven roles of NETs in the course of cancer with particular focus on the significance of NETs as prognosis biomarkers in the course of the neoplastic process and their potential use in therapy.

Neuroimmunoendocrine Interactions in Tumorigenesis and Breast Cancer

“…Thereafter, cytoplasmic granules in the neutrophil get fused with the phagolysosome where the microorganism is destroyed [52]. Under adverse circumstances, neutrophil can release proteinases through microbursts, to the extracellular space, or produce NETs to fix the microorganisms, stop their migration, and concentrate on toxic factors [56].…”

“…Cellular cytotoxic role in cancer is traditionally associated with cytotoxic T cells, NK cells, and macrophages, and little attention is focused on neutrophils, but nowadays, reports are linking neutrophils to different stages of cancer [56]. Naïve neutrophils are recruited to the tumor, mainly by macrophages, and display the same repertory to kill a microorganism for the destruction of a tumor cell, and eventually a pro-host or pro-tumoral effect in situ is developed (Figure 2) [52].…”

Could Neutrophil Extracellular Traps Be the New Prognostic Markers of Cancer?

“…Although the exact mechanism remains unknown, NETs have been described to trigger thrombogenicity and this phenomenon could be explained by neutrophils themselves and histone release but also due to the platelet trapping by NETs and the initiation of the formation of the thrombus 2,8 . In addition, some elements of NETs might induce platelet activation, accumulation of erythrocytes, and the release of von Willebrand factor, which is known as one of the main components of thrombus 8 . In vitro studies have shown that venous thrombi could be significantly reduced when NETs were targeted with NE inhibitor and DNAse I.…”

“…In vitro studies have shown that venous thrombi could be significantly reduced when NETs were targeted with NE inhibitor and DNAse I. Furthermore, data suggest that leukemia and cancer cells produced factors contributing to the formation of NETs, which were at the same time a predisposition for thrombosis 2,8 . The different currently accepted roles of NETs in cancer are summarized in figure 1.…”

Neutrophilic Extracellular Traps in Tissues With Different Treatment Modes of Colorectal Cancer

“…On the other hand, NET can promote migration and immune avoidance of tumor cells. The possible role of the flow of neoplastic process As a prognostic biomarker in NET is suggested [4,5]. The aim of this study was to investigate extracellular neutrophil traps in colorectal cancer.…”