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Journal of Immunology Research
Volume 2014, Article ID 659294, 12 pages
http://dx.doi.org/10.1155/2014/659294
Research Article

A Circulating Subpopulation of Monocytic Myeloid-Derived Suppressor Cells as an Independent Prognostic/Predictive Factor in Untreated Non-Small Lung Cancer Patients

1Laboratory of Cancer Cell Biology, School of Medicine, University of Crete, 71110 Heraklion, Crete, Greece
2Department of Medical Oncology, University Hospital of Heraklion, 71110 Heraklion, Crete, Greece

Received 10 July 2014; Revised 19 September 2014; Accepted 29 September 2014; Published 11 November 2014

Academic Editor: Jacek Tabarkiewicz

Copyright © 2014 Eleni-Kyriaki Vetsika et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of cells with immunosuppressive properties and might confer to worse prognosis in cancer patients. The presence of phenotypically newly described subpopulations of MDSCs and their association with the clinical outcome were investigated in non-small cell lung cancer (NSCLC) patients. The percentages and correlation between MDSCs and distinct immune cells in the peripheral blood of 110 chemotherapy-naive patients before treatment and healthy controls were investigated using flow cytometry. Two monocytic [CD14+CD15CD11b+CD33+HLA-DRLin and CD14+CD15+CD11b+CD33+HLA-DRLin] and a granulocytic [CD14CD15+CD11b+CD33+HLA-DRLin] subpopulations of MDSCs were identified, expressing inducible nitric oxide synthase, and reactive oxygen species, respectively. Increased percentages of both monocytic-MDSCs’ subpopulations were inversely correlated to dendritic/monocyte levels , while granulocytic-MDSCs were inversely correlated to CD4+ T cells . Increased percentages of monocytic-MDSCs were associated with worse response to treatment and patients with normal levels of CD14+CD15+CD11b+CD33+HLA-DRLin had longer overall survival and progression free-survival compared to those with high levels and , resp.). Multivariate analysis revealed that the increased percentages of CD14+CD15+CD11b+CD33+HLA-DRLin MDSCs were independently associated with decreased progression free-survival and overall survival. The data provide evidence that increased percentages of new monocytic-MDSCs’ subpopulations in advanced NSCLC patients are associated with an unfavourable clinical outcome.