Neutrophil extracellular traps and neutrophil-related mediators in human thyroid cancer

Frontiers in Immunology

Immunology

Silvia Martina Ferrari¹  Alessandro Antonelli²  Sabrina Rosaria Paparo²  Leonardo Cristinziano³  Maria Rosaria Galdiero³  Remo Poto³  Annagioia Ventrici³  Marialuisa Trocchia³  Luca Modestino³  Gianni Marone⁴  Gilda Varricchi⁴  Poupak Fallahi⁵ 

[1] Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy;Department of Translational Medical Sciences (DiSMeT), University of Naples Federico II, Naples, Italy;Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy;World Allergy Organization Center of Excellence, University of Naples Federico II, Naples, Italy;Department of Translational Medical Sciences (DiSMeT), University of Naples Federico II, Naples, Italy;Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy;World Allergy Organization Center of Excellence, University of Naples Federico II, Naples, Italy;Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy;Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy;

关键词: neutrophils;    neutrophil extracellular traps;    thyroid cancer;    dedifferentiated thyroid cancer;    NETs biomarkers;   

DOI  :  10.3389/fimmu.2023.1167404

 received in 2023-02-16, accepted in 2023-08-14,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundPolymorphonuclear neutrophils (PMNs) are the main effector cells in inflammatory responses and play multiple roles in thyroid cancer (TC). PMNs contain and release a plethora of mediators, including granular enzymes [e.g., myeloperoxidase (MPO), pentraxin-3 (PTX3) and matrix metalloproteinase-9 (MMP-9)], and neutrophil extracellular traps (NETs). The aim of this study was to evaluate NETs and neutrophil-derived mediators as possible biomarkers in TC patients.Methods20 patients with differentiated thyroid cancer (DTC), 26 patients with dedifferentiated thyroid cancer (De-DTC), 26 patients with multinodular goiter (MNG) and 22 healthy controls (HCs) were recruited. Serum concentrations of free DNA (dsDNA), nucleosomes, citrullinated histone H3 (CitH3) and MPO-DNA complexes were evaluated as NET biomarkers. Neutrophil-related mediators such as MPO, PTX3, MMP-9, CXCL8, and granulocyte-monocyte colony-stimulating factor (GM-CSF) were measured by ELISA.ResultsSerum levels of all four NET biomarkers were increased in DeDTC patients compared to HCs. CitH3 serum levels were selectively increased in both DeDTC and DTC patients compared to HCs and MNG patients. MPO-DNA complexes and nucleosomes were selectively increased only in DeDTC patients compared to HCs and MNG patients. Moreover, MPO-DNA complexes were selectively increased in DeDTC patients compared to DTC patients also. MPO circulating levels were selectively increased in the DeDTC patient subgroup compared to HCs. Circulating levels of PTX3, MMP-9 and GM-CSF were increased in DTC and DeDTC patients compared to HCs. Nucleosomes positively correlated with dsDNA, CitH3, MPO and CXCL8. MPO-DNA complexes positively correlated with dsDNA, CitH3, CXCL8, MPO and nucleosome levels. Moreover, three out of the four NET biomarkers (i.e., dsDNA, nucleosomes and MPO-DNA complexes) were increased in elderly patients compared to young patients and in patients with metastatic disease at diagnosis compared to non metastatic patients. Nucleosomes were higher in males compared to females.ConclusionMPO-DNA complexes, nucleosomes and, to some extent, CitH3 levels seem to correlate with malignancy and severity of progressive TC. Moreover, serum concentrations of PMN-related mediators (MPO, PTX3, GM-CSF) were increased in TCs compared to MNG and HCs.

【 授权许可】

Unknown   
Copyright © 2023 Modestino, Cristinziano, Poto, Ventrici, Trocchia, Ferrari, Fallahi, Paparo, Marone, Antonelli, Varricchi and Galdiero