Neutrophils in lung cancer patients: Activation potential and neutrophil extracellular trap formation

Lisa-Marie Mauracher; Lena Hell; Florian Moik; Moritz Krall; Cornelia Englisch; Johanna Roiß; Ella Grilz; Thomas M Hofbauer; Christine Brostjan; Sylvia Knapp; Cihan Ay; Ingrid Pabinger

doi:10.1016/j.rpth.2023.100126

Neutrophils in lung cancer patients: Activation potential and neutrophil extracellular trap formation

Res Pract Thromb Haemost. 2023 Mar 15;7(2):100126. doi: 10.1016/j.rpth.2023.100126. eCollection 2023 Feb.

Authors

Affiliations

¹ Department of Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University of Vienna, Austria.
² Department of Internal Medicine, Clinical Division of Oncology, Medical University of Graz, Graz, Austria.
³ Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Austria.
⁴ Department of General Surgery, Division of Vascular Surgery, Medical University of Vienna, Austria.
⁵ Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, Austria.

Abstract

Background: Patients with cancer have an increased risk of developing venous thromboembolism. Neutrophils and neutrophil extracellular traps (NETs) reportedly influence the risk of cancer-associated thrombosis. Subpopulations of high and low-density neutrophils (HDN/LDN) are of specific interest, as they might have different functions in cancer patients.

Objectives: We aimed to investigate differences between HDNs and LDNs of patients with lung cancer and healthy controls, and their ability of activation and NET formation.

Methods: Within the framework of the Vienna Cancer and Thrombosis Study, a prospective observational cohort study, HDNs and LDNs from 20 patients with lung cancer and 20 controls were isolated by density gradient centrifugation. The ability of neutrophil subpopulations for activation and NET formation was investigated by flow cytometry.

Results: Compared to controls, patients with cancer had higher numbers of total leukocytes, HDNs, and LDNs. LDNs of patients were more frequently in an activated state (CD62L↓/CD16↑) at baseline (median [IQR] 5.9% [3.4-8.8] vs 2.5% [1.6-6.7]). HDNs and LDNs from patients showed a significantly increased response to stimulation with ionomycin (CD11b HDN: 98.5 [95.4-99.4] vs 41.7 [13.4-91.6]; LDN: 82.9 [63-94] vs 39.6 [17.3-72.1]). In addition, HDNs from patients showed a higher capability of NET formation after ionomycin stimulation compared to HDNs from healthy controls (18509.5 [12242.5-29470.3] vs 10001 [6618.8-18384.3]).

Conclusion: Protumorigenic LDNs were elevated, and neutrophil subpopulations showed an increased activation profile and ability for NET formation in patients with cancer. These mechanisms might be involved in tumor promotion and contribute to the prothrombotic phenotype of neutrophils in cancer.

Keywords: cancer-associated thrombosis; high-density neutrophil; low-density neutrophil; lung cancer; neutrophil extracellular traps.