Abstract 3664: High frequency of a circulating monocytic subpopulation of myeloid-derived suppressor cells predicts worst clinical outcome in untreated non-small lung cancer patients
Authors: Vetsika Eleni Kyriaki , Koinis Filippos , Gioulmpasani Marianthi , Aggouraki Despoina , Koutoulaki Anna , Skalidaki Eirini , Mavroudis Dimitris , Georgoulias Vassilis , Kotsakis Athanasios 
Published: May 2015

Abstract
Background: The immune system can either prevent and control the tumor growth or promote tumor escape. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature cells with immune suppressive properties and their overexpression seems to confer a worse prognosis in cancer patients.
Objective: The aim of the study was to investigate the presence of new phenotypically immature subpopulations of MDSCs which could be associated with advanced/metastatic NSCLC patients' clinical outcome.
Materials & Methods: Circulating subtypes of MDSCs (monocytic and granulocytic), as well as the CD4+ , CD8+ , dendritic (DC), monocytes and B cells were assessed in peripheral blood of of chemotherapy-naive patients with advanced/metastatic NSCLC (n=134) and healthy controls (n=28) were analyzed using flow cytometry. The phenotypic characterization of MDSCs subpopulations was determined in strictly immature myeloid cells. A correlation between the levels of MDSCs and other tested immune cells as well as their association with overall (OS) and progression- free survival (PFS) was evaluated; high expression of MDSCs was defined as the percentage of the cells above the 90% percentile of the controls.
Results: Two monocytic [M-MDSC: CD14+CD15-CD11b+CD33+HLA-DR-Lin- and CD14+CD15+CD11b+CD33+HLA-DR-Lin-] and a granulocytic [G-MDSC: CD14-CD15+CD11b+CD33+HLA-DR-Lin-] subpopulation of MDSCs were significantly increased (p&lt;0.001), while the frequencies of CD4+ cells, DC and monocytes were decreased in patients compared to healthy donors (p≤0.0001, p≤0.0004, p=0.015; respectively). The frequency of both M-MDSCs' subpopulations was inversely correlated to that of DCs (p≤0.04), while the G-MDSC subpopulation was inversely correlated to CD4+ T cells (p=0.006). Furthermore, the M-MDSCs expressed high levels of iNOS, whereas the G-MDSCs generated high levels of reactive oxygen species (ROS). Increased frequencies of M-MDSCs were associated with worse response to front-line treatment (p=0.02) and patients with normal levels of CD14+CD15+CD11b+CD33+HLA-DR-Lin- MDSCs had longer OS and PFS compared to those with high levels (p=0.008 and p=0.02, respectively). Multivariate analysis revealed that the increased number of CD14+CD15+CD11b+CD33+HLA-DR-Lin- MDSCs was independently associated with decreased PFS and OS.
Conclusion: The data provide evidence that the increased frequency of two new M-MDSC subpopulations in patients with advanced/metastatic NSCLC is associated with an unfavorable clinical outcome.
Citation Format: Eleni Kyriaki Vetsika, Filippos Koinis, Marianthi Gioulmpasani, Despoina Aggouraki, Anna Koutoulaki, Eirini Skalidaki, Dimitris Mavroudis, Vassilis Georgoulias, Athanasios Kotsakis. High frequency of a circulating monocytic subpopulation of myeloid-derived suppressor cells predicts worst clinical outcome in untreated non-small lung cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3664. doi:10.1158/1538-7445.AM2014-3664