Emerging Role of Neutrophil Extracellular Traps in Gastrointestinal Tumors: A Narrative Review

Abstract

Neutrophil extracellular traps (NETs) are extracellular fibrous networks consisting of depolymerized chromatin DNA skeletons with a variety of antimicrobial proteins. They are secreted by activated neutrophils and play key roles in host defense and immune responses. Gastrointestinal (GI) malignancies are globally known for their high mortality and morbidity. Increasing research suggests that NETs contribute to the progression and metastasis of digestive tract tumors, among them gastric, colon, liver, and pancreatic cancers. This article explores the formation of NETs and reviews the role that NETs play in the gastrointestinal oncologic microenvironment, tumor proliferation and metastasis, tumor-related thrombosis, and surgical stress. At the same time, we analyze the qualitative and quantitative detection methods of NETs in recent years and found that NETs are specific markers of coronavirus disease 2019 (COVID-19). Then, we explore the possibility of NET inhibitors for the treatment of digestive tract tumor diseases to provide a new, efficient, and safe solution for the future therapy of gastrointestinal tumors.

Neutrophil hitchhiking: Riding the drug delivery wave to treat diseases

“…Neutrophils also secrete various cytokines, which modulate the activation and recruitment of monocyte‐macrophages and dendritic cells (Li et al, 2019). NETs serve as an important source of autoantigens, capable of activating T cells, B cells, macrophages, and the complement system (Zhang et al, 2023). In certain conditions, excessive production or impaired clearance of NETs can accelerate the inflammatory process, leading to immune responses and a decline in the body's ability to tolerate diseases (Zhu et al, 2023).…”

Targeting Neutrophil Extracellular Trap Formation: Exploring Promising Pharmacological Strategies for the Treatment of Preeclampsia

“…There are several signalling pathways involved in NET formation [48]; one pathway involves the generation of ROS through the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Activation of the NADPH oxidase complex 2 (NOX2) triggers the Raf/MEK/ERK pathway and augments cytosolic ROS levels [49], resulting in citrullinated histone H3-dependent (Cit-Histone H3) lytic or suicidal NETosis, Figure 1.…”

Tumor Microenvironment Remodeling in Gastrointestinal Cancer: Role of miRNAs as Biomarkers of Tumor Invasion

“…Tumor-associated neutrophils (TANs) play a controversial role in tumor progression. Although they are known to have antitumor activity, many studies have shown that the presence of TANs is associated with the promotion of tumor metastatic potential and poor prognosis in many tumor types [ 107 , 108 ]. Especially, type 2 TANs have immunosuppressive action characterized by the production of chemokines, some having a role in cancer cell migration, such as CCL2, CCL3, CCL4, CCL8, CXCL8, and CXCL16 [ 109 ].…”