title: Effect of First-Line Treatment on Myeloid-Derived Suppressor Cells' Subpopulations in the Peripheral Blood of Patients with Non-Small Cell Lung Cancer.
abstract: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature cells of myeloid origin whose expression is induced by, among others things, vascular endothelial growth factor. We have previously identified two monocytic and one granulocytic MDSC subpopulations associated with the clinical outcome in patients with non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate the effect of chemotherapy on these MDSC subpopulations.
  
  
  
  Circulating immune cells from 46 patients with unresectable NSCLC were analyzed by flow cytometry before the initiation of chemotherapy and after three cycles. Changes in the frequencies of the MDSC subpopulations were correlated with clinical outcome.
  
  
  
  Chemotherapy had no uniform effect on either the number or the functionality of monocytic and granulocytic MDSCs. However, three cycles of bevacizumab-containing regimens significantly reduced the percentage of the granulocytic-MDSCs compared with non-bevacizumab-based regimens (p = 0.0086). At the time of evaluation of response, disease progression was associated with significantly higher levels of all three MDSC subpopulations compared with in patients with disease control. Ιn patients with disease progression after three cycles of chemotherapy, the percentage of CD15-positive monocytic MDSCs was significantly increased compared with baseline.
  
  
  
  In the peripheral blood of patients with NSCLC, bevacizumab-based chemotherapy significantly reduced the levels of granulocytic MDSCs. An increase in the levels of CD15-positive monocytic MDSCs was associated with poor response to treatment and disease progression, providing evidence of their clinical relevance in patients with NSCLC.
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece; Department of Medical Oncology, University General Hospital of Heraklion, Voutes, Crete, Greece; Hellenic Oncology Research Group, Athens, Greece.
authors.forename: Filippos
authors.initials: F
authors.lastname: Koinis
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Eleni Kyriaki
authors.initials: EK
authors.lastname: Vetsika
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Despoina
authors.initials: D
authors.lastname: Aggouraki
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Skalidaki
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Koutoulaki
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Marianthi
authors.initials: M
authors.lastname: Gkioulmpasani
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece; Department of Medical Oncology, University General Hospital of Heraklion, Voutes, Crete, Greece; Hellenic Oncology Research Group, Athens, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece; Department of Medical Oncology, University General Hospital of Heraklion, Voutes, Crete, Greece; Hellenic Oncology Research Group, Athens, Greece. Electronic address: kotsakis@med.uoc.gr.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Kotsakis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000068258:Bevacizumab / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents; D016256:Lewis X Antigen / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000072737:Myeloid-Derived Suppressor Cells / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D016256:Lewis X Antigen; D018950:Lipopolysaccharide Receptors; D017382:Reactive Oxygen Species; D000068258:Bevacizumab
keywords: Bevacizumab-based regimen; Myeloid-derived suppressor cells; Non–small cell lung cancer; VEGF