Myeloid-derived suppressor cells are associated with disease progression and decreased overall survival in advanced-stage melanoma patients

Abstract

Myeloid-derived suppressor cells are increased in the peripheral blood of advanced-stage cancer patients; however, no studies have shown a correlation of these immunosuppressive cells with clinical outcomes in melanoma patients. We characterized the frequency and suppressive function of multiple subsets of myeloid-derived suppressor cells in the peripheral blood of 34 patients with Stage IV melanoma, 20 patients with Stage I melanoma, and 15 healthy donors. The frequency of CD14+ MDSCs (Lin− CD11b+ HLA-DR− CD14+ CD33+) and CD14− MDSCs (Lin− CD11b+ HLA-DR− CD14− CD33+) were increased in the peripheral blood of Stage IV melanoma patients relative to healthy donors. The frequency of CD14+ and CD14− MDSCs correlated with each other and with the increased frequency of regulatory T cells, but not with classically-defined monocytes. CD14− MDSCs isolated from the peripheral blood of Stage IV melanoma patients suppressed T cell activation more than those isolated from healthy donors and the frequency of these cells correlated with disease progression and decreased overall survival. Our study provides the first evidence that the frequency of CD14− 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.

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

“…On the other hand, cancer development has been associated with an increased percentage of MDSCs and Tregs (Jordan et al 2013;Kalathil et al 2013;Yu et al 2013). Chronic lymphocytic leukaemia (CLL) patients (69.4±8.5 years old) have been reported to have a significantly higher number of MDSCs (CD14 + HLA-DR low ) compared to healthy donors.…”

Immunoglobulin-like transcript 3 is expressed by myeloid-derived suppressor cells and correlates with survival in patients with non-small cell lung cancer

“…25,26 To validate this effect in our patient cohort, patients were divided into 2 groups based on the proportion of MDSCs. Values that were higher than the mean C 2SD of healthy controls were considered to be elevated.…”

Protection against HPV-16–Associated Tumors Requires the Activation of CD8+ Effector Memory T Cells and the Control of Myeloid-Derived Suppressor Cells

“…6, 7). MDSCs are found in increased levels in the blood of patients diagnosed with different cancer types, including head and neck, breast, non-small cell lung, renal, pancreatic, esophageal, gastric cancers, and melanoma (8)(9)(10)(11)(12). MDSCs, a heterogeneous population of immature myeloid cells, are capable of interfering with tumor immunity and promoting tumor growth by inhibiting natural killer (NK) cell cytotoxicity and CD4 þ and CD8 þ T-cell activation, as well as the activation and attraction of regulatory T cells (Treg), but their actual contribution in the performance of anticancer vaccines is largely unknown (13)(14)(15)(16).…”