Tumor-produced interleukin-8 attracts human myeloid-derived suppressor cells and elicits extrusion of neutrophil extracellular traps (NETs)
Alfaro C (1), Teijeira A (2), Oñate C (3), Perez G (4), Fernandez de Sanmamed M (5), Andueza MP (6), Alignani D (7), Labiano S (8), Azpilikueta A (8), Rodriguez-Paulete A (9), Garasa S (9), Fusco JP (10), Aznar MA (11), Inoges S (9), Medina-Echeverz J (9), Berraondo P (12), Perez-Gracia JL (10), Melero I (13).
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. IL-8 (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 IL-8, IL-8 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.
IL-8 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. IL-8 did not modify the T-cell suppressor activity of human MDSC. However, IL-8 induced the formation of NETs in the GrMDSC subset.
IL-8 derived from tumors contributes to the chemotactic recruitment of MDSC and to their functional control.
CITATION Clin Cancer Res. 2016 Mar 8. pii: clincanres.2463.2015.