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Review
. 2022 Mar 25;23(7):3573.
doi: 10.3390/ijms23073573.

Potential Role of Neutrophil Extracellular Traps in Cardio-Oncology

Kai-Hung Cheng  1   2 , Gregory P Contreras  3 , Ting-Yu Yeh  3
Affiliations
Review

Potential Role of Neutrophil Extracellular Traps in Cardio-Oncology

Kai-Hung Cheng et al. Int J Mol Sci. .

Abstract

Cardiovascular toxicity has emerged as the leading cause of death in patients undergoing cancer treatment. Thus, cardio-oncology (CO) care must also focus on the prevention and management of related cardiovascular (CV) complications caused by cancer therapy. Neutrophil extracellular traps (NETs)-entities with released DNA, proteases, proinflammatory and prooxidative substances from blasted neutrophils-play an important role in cancer proliferation, propagation metastasis, and incident CV events (acute coronary syndrome, thromboembolic events, and heart failure). Although NETs have been shown to be involved in cancer progression and incident CV events, little is known about their relationship with cardio-oncology, especially on cancer treatment-related cardiovascular toxicity (CTRCT). This review aims to explore the evidence of the impact of NETs on cancer, CV events, and CTRCT, and the possible solutions based on the mechanism of NETs activation and NETs released toxic substances.

Keywords: cancer therapeutics-related cardiovascular dysfunction (CTRCD); cancer treatment-related cardiovascular toxicity (CTRCT); cardio-oncology (CO); neutrophil extracellular traps (NETs).

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Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1
Figure 1
Summary of potential roles of neutrophil extracellular traps (NETs) in cancer treatment-related cardiovascular toxicity. Neutrophil extracellular traps (NETs) a, bearing DNA strands and released proteins containing myeloperoxidase, Cathepsin G, neutrophil elastase (NE), and proteinase 3 (PR3), a series of phospholipases, hypochlorous acid (HOCl) and pro-IL (interleukin)-1α; NETosis triggers b, including activated platelets while in contact with collagen, IL-8, TNF, pathogens, PMA…etc. Possible candidates for mitigating NETs burden to increase cancer survival and reduce cancer treatment-related cardiovascular toxicity (CTRCT) c: including (1) Potent anti-platelet therapy, (2) Deoxyribonuclease (DNase I), (3) Inhibition of peptidyl arginine deiminase-4 (PAD-4), (4) Inhibition of myeloperoxidase (MPO), (5) Anti-cytokine therapy (e.g., targeting IL-1 isoforms, IL-8, or IL-6), (6) Inhibition serine proteases.
Figure 2
Figure 2
The high IL-8 in tumor environment recruits neutrophil and enhances NETs formation, which causes resistance to immunotherapy. DNase I reverses this situation.
See this image and copyright information in PMC

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