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Increased Potential of Neutrophil Activation and Neutrophil Extracellular Trap Formation in Patients with Lung Cancer

1Medical University of Vienna, Hematology and Hemostaseology, Vienna, Austria, 2Medical University of Vienna, Department of Internal Medicine II, Division of Cardiology, Vienna, Austria, 3Medical University of Vienna, Department of Surgery, Vienna, Austria

Abstract Number: PB2118

Meeting: ISTH 2020 Congress

Theme: Venous Thromboembolism and Cardioembolism » Cancer Associated Thrombosis

Background: Neutrophil heterogeneity and newly discovered functions are important foci of neutrophil research. Neutrophil extracellular traps (NETs) have been shown to be associated with thrombotic risk in patients with cancer. Neutrophil subpopulations, high and low density neutrophils (HDN/LDN) may have different roles with different abilities to undergo NET formation and thus promote thrombosis.

Aims: We aimed to investigate differences in neutrophil subpopulations, their potential of activation and NET formation between patients with cancer and healthy controls.

Methods: HDNs and LDNs from 20 patients with lung cancer (median age 67 years, range 46-82, 55% female) enrolled in the Vienna Cancer and Thrombosis Study (CATS) prior to anti-cancer treatment were isolated by density gradient centrifugation. 20 healthy individuals (62 years (50-72), 55% female) served as controls. Potential of activation (increase of CD11b surface expression) and NET formation (citrullination of histone H3 (H3Cit)) were investigated via flow cytometry. Cells were stimulated with ionomycin (IO) and phorbol 12-myristate 13-acetate (PMA). The percentage of CD11bhigh cells (according to baseline set to 1%) and median fluorescent intensity (MFI) of H3Cit were analysed.

Results: Comparison of neutrophil subpopulations isolated from patients and controls revealed 2-fold higher LDN numbers (patients median 71×103/mL blood (IQR 47×103-130×103), controls 37×103 (21×103-55×103), p< 0.001) (Fig.1A). HDNs and LDNs from patients with cancer had a significantly higher potential of activation after 30min stimulation (Fig.1B/C). H3Cit production was increased in HDNs from patients with cancer compared to HDNs from control individuals (Fig.1D), whereas no differences in LDNs were observed between cohorts (data not shown).

Conclusions: Patients with cancer have more LDNs. HDNs and LDNs show a higher potential of activation and HDNs have a higher NET production, reflected by H3Cit. We conclude that neutrophil subpopulations, each in a specific way, may contribute to the increased risk of thrombosis in patients with cancer.


[igure 1: Cancer patients versus healthy controls: LDN count (A), increase of CD11b high in HDNs (B) and LDNs (C), increase of MFI H3Cit in HDNs (D)]

To cite this abstract in AMA style:

Mauracher L-, Krall M, Moik F, Hell L, Roiß J, Hofbauer TM, Brostjan C, Ay C, Pabinger I. Increased Potential of Neutrophil Activation and Neutrophil Extracellular Trap Formation in Patients with Lung Cancer [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/increased-potential-of-neutrophil-activation-and-neutrophil-extracellular-trap-formation-in-patients-with-lung-cancer/. Accessed September 29, 2023.

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