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

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 wer...

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Main Authors: Eleni-Kyriaki Vetsika, Filippos Koinis, Marianthi Gioulbasani, Despoina Aggouraki, Anna Koutoulaki, Eirini Skalidaki, Dimitris Mavroudis, Vassilis Georgoulias, Athanasios Kotsakis
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2014/659294
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author Eleni-Kyriaki Vetsika
Filippos Koinis
Marianthi Gioulbasani
Despoina Aggouraki
Anna Koutoulaki
Eirini Skalidaki
Dimitris Mavroudis
Vassilis Georgoulias
Athanasios Kotsakis
author_facet Eleni-Kyriaki Vetsika
Filippos Koinis
Marianthi Gioulbasani
Despoina Aggouraki
Anna Koutoulaki
Eirini Skalidaki
Dimitris Mavroudis
Vassilis Georgoulias
Athanasios Kotsakis
author_sort Eleni-Kyriaki Vetsika
collection DOAJ
description 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+CD15−CD11b+CD33+HLA-DR−Lin− and CD14+CD15+CD11b+CD33+HLA-DR−Lin−] and a granulocytic [CD14−CD15+CD11b+CD33+HLA-DR−Lin−] 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 (P≤0.04), while granulocytic-MDSCs were inversely correlated to CD4+ T cells (P=0.006). Increased percentages of monocytic-MDSCs were associated with worse response to treatment (P=0.02) and patients with normal levels of CD14+CD15+CD11b+CD33+HLA-DR−Lin− had longer overall survival and progression free-survival compared to those with high levels (P=0.008 and P=0.005, resp.). Multivariate analysis revealed that the increased percentages of CD14+CD15+CD11b+CD33+HLA-DR−Lin− 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.
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spelling doaj-art-b3d05d02fa034335a35450e91afab8742025-02-03T01:03:34ZengWileyJournal of Immunology Research2314-88612314-71562014-01-01201410.1155/2014/659294659294A Circulating Subpopulation of Monocytic Myeloid-Derived Suppressor Cells as an Independent Prognostic/Predictive Factor in Untreated Non-Small Lung Cancer PatientsEleni-Kyriaki Vetsika0Filippos Koinis1Marianthi Gioulbasani2Despoina Aggouraki3Anna Koutoulaki4Eirini Skalidaki5Dimitris Mavroudis6Vassilis Georgoulias7Athanasios Kotsakis8Laboratory of Cancer Cell Biology, School of Medicine, University of Crete, 71110 Heraklion, Crete, GreeceDepartment of Medical Oncology, University Hospital of Heraklion, 71110 Heraklion, Crete, GreeceLaboratory of Cancer Cell Biology, School of Medicine, University of Crete, 71110 Heraklion, Crete, GreeceLaboratory of Cancer Cell Biology, School of Medicine, University of Crete, 71110 Heraklion, Crete, GreeceLaboratory of Cancer Cell Biology, School of Medicine, University of Crete, 71110 Heraklion, Crete, GreeceLaboratory of Cancer Cell Biology, School of Medicine, University of Crete, 71110 Heraklion, Crete, GreeceLaboratory of Cancer Cell Biology, School of Medicine, University of Crete, 71110 Heraklion, Crete, GreeceLaboratory of Cancer Cell Biology, School of Medicine, University of Crete, 71110 Heraklion, Crete, GreeceLaboratory of Cancer Cell Biology, School of Medicine, University of Crete, 71110 Heraklion, Crete, GreeceMyeloid-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+CD15−CD11b+CD33+HLA-DR−Lin− and CD14+CD15+CD11b+CD33+HLA-DR−Lin−] and a granulocytic [CD14−CD15+CD11b+CD33+HLA-DR−Lin−] 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 (P≤0.04), while granulocytic-MDSCs were inversely correlated to CD4+ T cells (P=0.006). Increased percentages of monocytic-MDSCs were associated with worse response to treatment (P=0.02) and patients with normal levels of CD14+CD15+CD11b+CD33+HLA-DR−Lin− had longer overall survival and progression free-survival compared to those with high levels (P=0.008 and P=0.005, resp.). Multivariate analysis revealed that the increased percentages of CD14+CD15+CD11b+CD33+HLA-DR−Lin− 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.http://dx.doi.org/10.1155/2014/659294
spellingShingle Eleni-Kyriaki Vetsika
Filippos Koinis
Marianthi Gioulbasani
Despoina Aggouraki
Anna Koutoulaki
Eirini Skalidaki
Dimitris Mavroudis
Vassilis Georgoulias
Athanasios Kotsakis
A Circulating Subpopulation of Monocytic Myeloid-Derived Suppressor Cells as an Independent Prognostic/Predictive Factor in Untreated Non-Small Lung Cancer Patients
Journal of Immunology Research
title A Circulating Subpopulation of Monocytic Myeloid-Derived Suppressor Cells as an Independent Prognostic/Predictive Factor in Untreated Non-Small Lung Cancer Patients
title_full A Circulating Subpopulation of Monocytic Myeloid-Derived Suppressor Cells as an Independent Prognostic/Predictive Factor in Untreated Non-Small Lung Cancer Patients
title_fullStr A Circulating Subpopulation of Monocytic Myeloid-Derived Suppressor Cells as an Independent Prognostic/Predictive Factor in Untreated Non-Small Lung Cancer Patients
title_full_unstemmed A Circulating Subpopulation of Monocytic Myeloid-Derived Suppressor Cells as an Independent Prognostic/Predictive Factor in Untreated Non-Small Lung Cancer Patients
title_short A Circulating Subpopulation of Monocytic Myeloid-Derived Suppressor Cells as an Independent Prognostic/Predictive Factor in Untreated Non-Small Lung Cancer Patients
title_sort circulating subpopulation of monocytic myeloid derived suppressor cells as an independent prognostic predictive factor in untreated non small lung cancer patients
url http://dx.doi.org/10.1155/2014/659294
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