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. 2013 Mar 6:4:48.
doi: 10.3389/fimmu.2013.00048. eCollection 2013.

A proposed role for neutrophil extracellular traps in cancer immunoediting

Sivan Berger-Achituv  1 , Volker Brinkmann, Ulrike Abu Abed, Lars I Kühn, Jonathan Ben-Ezra, Ronit Elhasid, Arturo Zychlinsky
Affiliations

A proposed role for neutrophil extracellular traps in cancer immunoediting

Sivan Berger-Achituv et al. Front Immunol. .

Abstract

Upon activation, neutrophils release fibers composed of chromatin and neutrophil proteins termed neutrophil extracellular traps (NETs). NETs trap and kill microbes, activate dendritic cells and T cells, and are implicated in autoimmune and vascular diseases. Given the growing interest in the role of neutrophils in cancer immunoediting and the diverse function of NETs, we searched for NETs release by tumor-associated neutrophils (TANs). Using pediatric Ewing sarcoma (ES) as a model, we retrospectively examined histopathological material from diagnostic biopsies of eight patients (mean ± SD age of 11.5 ± 4.7 years). TANs were found in six patients and in two of those we identified NETs. These two patients presented with metastatic disease and despite entering complete remission after intensive chemotherapy had an early relapse. NETs were not identified in the diagnostic biopsies of two patients with localized disease and two with metastatic disease. This study is the first to show that TANs in ES are activated to make NETs, pointing to a possible role of NETs in cancer.

Keywords: Ewing sarcoma; cancer; cancer immunoediting; neutrophil extracellular traps; neutrophils.

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Figures

FIGURE 1
FIGURE 1
Neutrophil extrcellular traps (NETs) in Ewing sarcoma. The histological HE stained sections of two patients in low (A,E) and high (B,F) magnification suggest the presence of NETs (thick black arrows). Immunofluorescence staining for myeloperoxidase (MPO; green), CD99 (blue), and DNA (red) of sections adjacent to those shown in HE at low (C,G) and high (D,H) magnification shows projections of a z-stack of confocal sections 5-μm thick. Naïve Neutrophils are located where MPO is in granules (thick white arrows). Neutrophils in the process of making NETs are found where MPO is localized to delobulated nuclei (thin white arrows) and NETs are located where MPO is colocalized with extracellular DNA (white arrowheads; scale bars, 25 μm).
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