Increased frequencies of CD11b⁺CD33⁺CD14⁺HLA‐DR^low myeloid‐derived suppressor cells are an early event in melanoma patients

Abstract

Myeloid-derived suppressor cells (MDSC) are a heterogeneous cell population characterized by immunosuppressive activity. Elevated levels of MDSC in peripheral blood are found in inflammatory diseases as well as in malignant tumors where they are supposed to be major contributors to mechanisms of tumor-associated tolerance. We investigated the frequency and function of MDSC in peripheral blood of melanoma patients and observed an accumulation of CD11b + CD33 + CD14 + HLA-DR low MDSC in all stages of disease (I-IV), including early stage I patients. Disease progression and enhanced tumor burden did not result in a further increase in frequencies or change in phenotype of MDSC. By investigation of specific MDSC-associated cytokines in patients' sera, we found an accumulation of IL-8 in all stages of disease. T-cell proliferation assays revealed that MDSC critically contribute to suppressed antigen-specific T-cell reactivity and thus might explain the frequently observed transient effects of immunotherapeutic strategies in melanoma patients.

Immune independent crosstalk between lymphoma and myeloid suppressor CD14+HLA-DRlow/negmonocytes mediates chemotherapy resistance

“…S1). Similar to studies in other cancer types, [8][9][10][11][12] we found that increased presence of CD14 C HLA-DR low/neg monocytes in lymphoma correlated with increased disease burden, worse treatment response and decreased survival. 5,13 In addition, decreased presence of these cells is associated with improved clinical response to treatments.…”

Clinical Significance of Circulating CD33+CD11b+HLA-DR− Myeloid Cells in Patients with Stage IV Melanoma Treated with Ipilimumab

“…In contrast with mice, human MDSCs lack the Gr1-like antigen and are still being characterized both biologically and phenotypically. However, as previously shown by others and us, the use of CD33 þ CD11b þ HLA-DR À to define MDSCs in various types of cancer has become very common (11,(15)(16)(17)(18). Within this CD33 þ population, the CD14 þ CD15 low/À CD11b þ MDSCs share characteristic similar to the murine monocytic MDSCs, whereas the CD14 À CD15 þ CD11b þ MDSCs resemble the murine granulocytic subtype (11,12).…”

“…S1A; refs. 15,17,18,24). Analysis of blood samples taken before the first ipilimumab treatment showed that the percentages of CD33 þ CD11b þ HLA-DR À MDSCs in the group of patients with melanoma was significantly higher (48.8 AE 2.3, P < 0.0001) as compared with HD (27.9 AE 1.7; Fig.…”

“…In the course of our analysis, we used a flow cytometry test to detect CD33 þ CD11b þ HLA-DR À MDSC frequencies in whole-blood frozen samples; unlike many of the published studies, which used a Ficoll density gradient centrifugation step for peripheral blood mononuclear cells (PBMCs) preparation, before freezing the samples and evaluating MDSC frequencies (9,17,(19)(20)(21). To determine the effect of cryopreservation/thawing and Ficoll centrifugation on MDSCs as well as on T-cell frequency, blood samples from 15 HD were analyzed.…”

Whole cell melanoma vaccine genetically modified to stem cells like phenotype generates specific immune responses to ALDH1A1 and long-term survival in advanced melanoma patients

“…44 Recently Rudolph et al observed accumulation of CD11b + CD33 + CD14 + HLA-DR −/low MDSCs in all stages of melanoma, including early stage I patients. 45 Moreover, circulating monocytic MDSCs were reported to have the negative impact on survival in patients with advanced melanoma and have independent prognostic value. 46,47 Furthermore, MDSCs inversely correlated with the presence of functional antigen-specific T cells and patients with high MDSCs levels had more PD-L1 T cells and more CTLA-4 expression by regulatory T cells.…”