Myeloid-derived suppressor cells are increased in the peripheral blood of advanced-stage cancer patients and prevent effective antitumor immune responses. Although these cells have been well characterized in mouse studies, few studies have shown a correlation of these immunosuppressive cells with functional and clinical outcomes in melanoma patients. We characterized the frequency and suppressive function of two subsets of myeloid-derived suppressor cells in the peripheral blood of 34 patients with Stage IV melanoma. The frequency of CD14+ MDSCs (Lin- CD11b+ HLA-DR- CD14+) and CD33+ MDSCs (Lin- CD11b+ HLA-DR- CD14- CD33+) were increased in the peripheral blood of Stage IV melanoma patients relative to healthy donors. These frequencies correlated with increased expression of PD-1 on peripheral T cells and an increased frequency of regulatory T cells. CD33+ MDSCs isolated from the peripheral blood of Stage IV melanoma patients, but not healthy donors, suppressed T cell activation and the frequency of these cells correlated with disease progression and decreased overall survival. Our study provides evidence that the frequency of CD33+ MDSCs negatively correlates with clinical outcomes in advanced-stage melanoma patients. These data indicate that suppressive MDSCs should be considered as targets for future immunotherapies.
- Copyright © 2013 by The American Association of Immunologists, Inc.