Abstract
Purpose: Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of pathologically expanded myeloid cells with immunosuppressive activity. In human disease, three major MDSC subpopulations can be defined as monocytic (M-MDSC), granulocytic [polymorphonuclear-MDSC (PMN-MDSC)], and early stage (e-MDSC), which lacks myeloid lineage markers of the former two subsets. The purpose of this study was to determine and compare the immunosuppressive capacity and clinical relevance of each of these subsets in patients with solid cancer.Experimental Design: The frequency of MDSC subsets in the peripheral blood was determined by flow cytometry in a cohort of 49 patients with advanced head and neck cancer (HNC) and 22 patients with urological cancers. Sorted and purified MDSC subsets were tested in vitro for their T-cell-suppressive capacity. Frequency of circulating MDSC was correlated with overall survival of patients with HNC.Results: A high frequency of PMN-MDSC most strongly correlated with poor overall survival in HNC. T-cell-suppressive activity was higher in PMN-MDSC compared with M-MDSC and e-MDSC. A subset of CD66b+/CD11b+/CD16+ mature PMN-MDSC displayed high expression and activity of arginase I, and was superior to the other subsets in suppressing proliferation and cytokine production of T cells in both cancer types. High levels of this CD11b+/CD16+ PMN-MDSC, but not other PMN-MDSC subsets, strongly correlated with adverse outcome in HNC.Conclusions: A subset of mature CD11b+/CD16+ PMN-MDSC was identified as the MDSC subset with the strongest immunosuppressive activity and the highest clinical relevance. Clin Cancer Res; 24(19); 4834-44. ©2018 AACR.
Highlights
Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of myeloid cells with immunosuppressive and tumorpromoting activity [1]
T-cell–suppressive activity was higher in PMN-MDSC compared with M-MDSC and Early-stage MDSC (e-MDSC)
PMN-MDSC was identified as the MDSC subset with the strongest immunosuppressive activity and the highest clinical relevance
Summary
Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of myeloid cells with immunosuppressive and tumorpromoting activity [1]. MDSC were defined in tumor-bearing mice, where two major subsets exist in blood, lymphoid organs, and tumor tissue. These two subsets are defined as Ly6Gþ granulocytic [polymorphonuclear-MDSC (PMN-MDSC)] and Ly6Cþ monocytic (M-MDSC) [2]. Suppression of T-cell activity is the hallmark of MDSC function, and the cells exploit an arsenal of molecules and mechanisms to downregulate T-cell function. The relative usage and importance of this arsenal are species, tissue, cell-type, and context dependent [3]. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/)
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