Neutrophil extracellular trap formation correlates with improved overall survival in ovarian cancer

Abstract

It is still a question of debate whether neutrophils, often found in the tumor microenvironment, mediate tumor-promoting or rather tumor-inhibiting activities. The present study focusses on the involvement of neutrophils in high grade serous ovarian cancer (HGSOC). Multi-omics data comprising proteomics, eicosadomics, metabolomics, Luminex-based cytokinomics, and FACS data were generated from ascites samples.Integrated data analysis demonstrates a significant increase of neutrophil extracellular trap-(NET) associated molecules in non-miliary ascites samples. A co-association network analysis performed with the ascites data further revealed a striking co-correlation between NETosisassociated metabolites with several eicosanoids. Investigating primary neutrophils from healthy domors, NET formation was induced using ionomycin or phorbol ester. Data congruence with ascites analyses indicated the predominance of NOX-independent NETosis.NETosis is associated with S100A8/A9 release. An increase of the S100A8/CRP abundance ratio was found to correlate with improved survival of HGSOC patients. The analysis of additional five independent proteome studies with regard to S100A8/CRP ratios confirmed this observation. In conclusion, here we present evidence that increased NET formation relates to improved outcomes in cancer patients.

Identification of the key immune-related genes in aneurysmal subarachnoid hemorrhage

“…For example, NET-S100A9-MMP9 acts as a critical component in connective tissue destruction (Akiyama et al, 2019). Levels of NET protein and S100A8 have also been shown to be important markers for predicting the prognosis of patients with ovarian cancer (Muqaku et al, 2020).…”

Identification and analysis of chemokine-related and NETosis-related genes in acute pancreatitis to develop a predictive model

“…In a recent study, NETs were identified as an effector function of neutrophils, characterized by extracellular networks of chromatin coated with histones, myeloperoxidase, and neutrophil elastase (Colón et al, 2019;Zhang et al, 2020). Neutrophils carry out their physiological roles through mechanisms such as phagocytosis, degranulation, and the release of NETs (Muqaku et al, 2020). The process of NET formation has been identified as a novel form of neutrophil cell death known as NETosis (Cho and Cho, 2019;Chen et al, 2022).…”

A novel tumor-immune microenvironment (TIME)-on-Chip mimics three dimensional neutrophil-tumor dynamics and neutrophil extracellular traps (NETs)-mediated collective tumor invasion

“…Conversely, chemotherapy induced neutropenia has also predicted improved survival rates among cancer patients [12][13][14][15][16][17], thereby raising important questions on the impact of neutrophils in tumor development. In the context of tumor metastasis, research has produced conflicting data in explaining whether neutrophils could promote the metastatic cascade [18][19][20][21][22], or support immune reactions inhibiting tumor growth [23][24][25][26]. A fuller understanding of the multifaceted neutrophil functionalities in tumorigenesis is still evolving [27], but there is a steadily growing appreciation that neutrophils can provide critical insights that are essential to tailor suitable anti-tumor and immunotherapeutic strategies, complementary to current therapeutic approaches [4,[28][29][30].…”