Tumor-Produced Interleukin-8 Attracts Human Myeloid-Derived Suppressor Cells and Elicits Extrusion of Neutrophil Extracellular Traps (NETs)

Clinical Cancer Research - Tập 22 Số 15 - Trang 3924-3936 - 2016
Carlos Alfaro1,2,3, Álvaro Teijeira1,2,3, Carmen Oñate1,2,3, Guiomar Pérez1,2,3, Miguel F. Sanmamed4,3, Maria Pilar Andueza4,3, Diego Alignani5, Sara Labiano6, Arantza Azpilikueta6, Alfonso Rodriguez-Paulete6, Saray Garasa6, Juan P. Fusco4,3, Ángela Aznar6, Susana Inogés4,3, Maria De Pizzol7, Marcello Allegretti7, José Medina‐Echeverz6, Pedro Berraondo6, Jose Luis Pérez‐Gracia4,3, Ignacio Melero1,2,3
11Division of Gene Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain.; 2Department of Oncology, University Clinic of Navarra, Pamplona, Spain.; 3Department of Immunology, University Clinic of Navarra, Pamplona, Spain.
22Department of Oncology, University Clinic of Navarra, Pamplona, Spain.
33Department of Immunology, University Clinic of Navarra, Pamplona, Spain.
42Department of Oncology, University Clinic of Navarra, Pamplona, Spain.; 3Department of Immunology, University Clinic of Navarra, Pamplona, Spain.
54Cytometry Platform, Centre for Applied Medical Research (CIMA), Pamplona, Spain.
61Division of Gene Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain.
75Dompé Farmaceutici SpA, L'Aquila, Italy.

Tóm tắt

Abstract Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: 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.

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Clinical Cancer Research

Tập 22 Số 15

3924-3936

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