期刊
CLINICAL CANCER RESEARCH
卷 22, 期 15, 页码 3924-3936出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-15-2463
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资金
- MICINN [SAF2011-22831, SAF2014-52361-R]
- Departamento de Salud del Gobiemo de Navarra
- Redes tematicas de investigacion cooperative RETICC
- European Commission VII Framework and Horizon 2020 programs (AICR and PROCROP)
- SUDOE-IMMUNONET
- Fundacion de la Asociacion Espanola Contra el Cancer (AECC)
- Fundacion Mutua Madrileria
- Fundacion BBVA
- Fundacion Caja Navarra
- Ministerio de Economia
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 MDSCand to their functional control. (C) 2016 AACR.
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