title: Tumor-Produced Interleukin-8 Attracts Human Myeloid-Derived Suppressor Cells and Elicits Extrusion of Neutrophil Extracellular Traps (NETs).
abstract: Myeloid-derived suppressor cells (MDSC) are considered an important T-cell immunosuppressive component in cancer-bearing hosts. The factors that attract these cells to the tumor microenvironment are poorly understood. IL8 (CXCL8) is a potent chemotactic factor for neutrophils and monocytes.
  
  
  
  MDSC were characterized and sorted by multicolor flow cytometry on ficoll-gradient isolated blood leucokytes from healthy volunteers (n = 10) and advanced cancer patients (n = 28). In chemotaxis assays, sorted granulocytic and monocytic MDSC were tested in response to recombinant IL8, IL8 derived from cancer cell lines, and patient sera. Neutrophil extracellular traps (NETs) formation was assessed by confocal microscopy, fluorimetry, and time-lapse fluorescence confocal microscopy on short-term MDSC cultures.
  
  
  
  IL8 chemoattracts both granulocytic (GrMDSC) and monocytic (MoMDSC) human MDSC. Monocytic but not granulocytic MDSC exerted a suppressor activity on the proliferation of autologous T cells isolated from the circulation of cancer patients. IL8 did not modify the T-cell suppressor activity of human MDSC. However, IL8 induced the formation of NETs in the GrMDSC subset.
  
  
  
  IL8 derived from tumors contributes to the chemotactic recruitment of MDSC and to their functional control. Clin Cancer Res; 22(15); 3924-36. ©2016 AACR.
authors.affiliation: Division of Gene Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain. Department of Oncology, University Clinic of Navarra, Pamplona, Spain. Department of Immunology, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Alfaro
authors.affiliation: Division of Gene Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain. Department of Oncology, University Clinic of Navarra, Pamplona, Spain. Department of Immunology, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Teijeira
authors.affiliation: Division of Gene Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain. Department of Oncology, University Clinic of Navarra, Pamplona, Spain. Department of Immunology, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Oñate
authors.affiliation: Division of Gene Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain. Department of Oncology, University Clinic of Navarra, Pamplona, Spain. Department of Immunology, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Guiomar
authors.initials: G
authors.lastname: Pérez
authors.affiliation: Department of Oncology, University Clinic of Navarra, Pamplona, Spain. Department of Immunology, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Miguel F
authors.initials: MF
authors.lastname: Sanmamed
authors.affiliation: Department of Oncology, University Clinic of Navarra, Pamplona, Spain. Department of Immunology, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Maria Pilar
authors.initials: MP
authors.lastname: Andueza
authors.affiliation: Cytometry Platform, Centre for Applied Medical Research (CIMA), Pamplona, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Alignani
authors.affiliation: Division of Gene Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Labiano
authors.affiliation: Division of Gene Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain.
authors.forename: Arantza
authors.initials: A
authors.lastname: Azpilikueta
authors.affiliation: Division of Gene Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Rodriguez-Paulete
authors.affiliation: Division of Gene Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain.
authors.forename: Saray
authors.initials: S
authors.lastname: Garasa
authors.affiliation: Department of Oncology, University Clinic of Navarra, Pamplona, Spain. Department of Immunology, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Fusco
authors.affiliation: Division of Gene Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Aznar
authors.affiliation: Department of Oncology, University Clinic of Navarra, Pamplona, Spain. Department of Immunology, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Inogés
authors.affiliation: Dompé Farmaceutici SpA, L'Aquila, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: De Pizzol
authors.affiliation: Dompé Farmaceutici SpA, L'Aquila, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Allegretti
authors.affiliation: Division of Gene Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Medina-Echeverz
authors.affiliation: Division of Gene Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Berraondo
authors.affiliation: Department of Oncology, University Clinic of Navarra, Pamplona, Spain. Department of Immunology, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Perez-Gracia
authors.affiliation: Division of Gene Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain. Department of Oncology, University Clinic of Navarra, Pamplona, Spain. Department of Immunology, University Clinic of Navarra, Pamplona, Spain. imelero@unav.es.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Melero
mesh_terms: D000818:Animals; D015415:Biomarkers; D045744:Cell Line, Tumor; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D004195:Disease Models, Animal; D065206:Extracellular Traps / Q000276:immunology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D000072737:Myeloid-Derived Suppressor Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000276:immunology*; D013449:Sulfonamides / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016209:Interleukin-8; D013449:Sulfonamides; C490707:reparixin