Heterogenous presence of neutrophil extracellular traps in human solid tumours is partially dependent on IL-8.

Autor: de Andrea CE; Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.; Department of Anatomy, Physiology and Pathology, University of Navarra, Pamplona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., Ochoa MC; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain., Villalba-Esparza M; Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., Teijeira Á; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IdISNA), Pamplona, Spain., Schalper KA; Department of Pathology, Yale University School of Medicine, New Haven, CT, USA., Abengozar-Muela M; Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.; Department of Anatomy, Physiology and Pathology, University of Navarra, Pamplona, Spain., Eguren-Santamaría I; Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.; Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain., Sainz C; Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain., Sánchez-Gregorio S; Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain., Garasa S; Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IdISNA), Pamplona, Spain., Ariz M; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Navarra Institute for Health Research (IdISNA), Pamplona, Spain., Ortiz-de-Solorzano C; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Navarra Institute for Health Research (IdISNA), Pamplona, Spain., Rodriguez-Ruiz ME; Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.; Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain., Perez-Gracia JL; Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain., Lozano MD; Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.; Department of Anatomy, Physiology and Pathology, University of Navarra, Pamplona, Spain., Echeveste JI; Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.; Department of Anatomy, Physiology and Pathology, University of Navarra, Pamplona, Spain., Sanmamed MF; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IdISNA), Pamplona, Spain.; Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain., Melero I; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IdISNA), Pamplona, Spain.
Jazyk: angličtina
Zdroj: The Journal of pathology [J Pathol] 2021 Oct; Vol. 255 (2), pp. 190-201. Date of Electronic Publication: 2021 Aug 05.
DOI: 10.1002/path.5753
Abstrakt: Neutrophil extracellular traps (NETs) are webs of extracellular nuclear DNA extruded by dying neutrophils infiltrating tissue. NETs constitute a defence mechanism to entrap and kill fungi and bacteria. Tumours induce the formation of NETs to the advantage of the malignancy via a variety of mechanisms shown in mouse models. Here, we investigated the presence of NETs in a variety of human solid tumours and their association with IL-8 (CXCL8) protein expression and CD8 + T-cell density in the tumour microenvironment. Multiplex immunofluorescence panels were developed to identify NETs in human cancer tissues by co-staining with the granulocyte marker CD15, the neutrophil marker myeloperoxidase and citrullinated histone H3 (H3Cit), as well as IL-8 protein and CD8 + T cells. Three ELISA methods to detect and quantify circulating NETs in serum were optimised and utilised. Whole tumour sections and tissue microarrays from patients with non-small cell lung cancer (NSCLC; n = 14), bladder cancer (n = 14), melanoma (n = 11), breast cancer (n = 31), colorectal cancer (n = 20) and mesothelioma (n = 61) were studied. Also, serum samples collected retrospectively from patients with metastatic melanoma (n = 12) and NSCLC (n = 34) were ELISA assayed to quantify circulating NETs and IL-8. NETs were detected in six different human cancer types with wide individual variation in terms of tissue density and distribution. At least in NSCLC, bladder cancer and metastatic melanoma, NET density positively correlated with IL-8 protein expression and inversely correlated with CD8 + T-cell densities. In a series of serum samples from melanoma and NSCLC patients, a positive correlation between circulating NETs and IL-8 was found. In conclusion, NETs are detectable in formalin-fixed human biopsy samples from solid tumours and in the circulation of cancer patients with a considerable degree of individual variation. NETs show a positive association with IL-8 and a trend towards a negative association with CD8 + tumour-infiltrating lymphocytes. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
(© 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.)
Databáze: MEDLINE
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