title: Myeloid derived suppressor cells are numerically, functionally and phenotypically different in patients with multiple myeloma.
abstract: Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of cells that have been implicated as inhibitors of lymphopoiesis in patients with malignancies. They have a consensus phenotype of CD33+/CD11b+/HLA-DRlo/- and can be further divided into CD15 + granulocytic (G-MDSC) and CD14 + monocytic (M-MDSC) subsets. We characterized MDSCs in patients with multiple myeloma (MM) and found a significant increase in G-MDSCs in the blood of patients with progressive MM. Flow-sorted MDSCs from patients with MM induced the generation of regulatory T cells (Treg). MDSCs from both patients with MM and aged-matched controls demonstrated a dose-dependent inhibition of lymphocyte proliferation in carboxyfluorescein succinimidyl ester (CFSE)-tracking experiments. Granulocyte colony stimulating factor (G-CSF) administered to induce stem cell mobilization caused an increase in the number of MDSCs in the peripheral blood of patients with MM and a concentration of these immune-suppressive cells in peripheral blood stem cell collections. MDSCs are likely to cause immune dysfunction in patients with MM.
authors.affiliation: Institute of Haematology, Royal Prince Alfred Hospital , Sydney, NSW , Australia.
authors.forename: James
authors.initials: J
authors.lastname: Favaloro
authors.forename: Tulita
authors.initials: T
authors.lastname: Liyadipitiya
authors.forename: Ross
authors.initials: R
authors.lastname: Brown
authors.forename: Shihong
authors.initials: S
authors.lastname: Yang
authors.forename: Hayley
authors.initials: H
authors.lastname: Suen
authors.forename: Narelle
authors.initials: N
authors.lastname: Woodland
authors.forename: Najah
authors.initials: N
authors.lastname: Nassif
authors.forename: Derek
authors.initials: D
authors.lastname: Hart
authors.forename: Phillip
authors.initials: P
authors.lastname: Fromm
authors.forename: Claire
authors.initials: C
authors.lastname: Weatherburn
authors.forename: John
authors.initials: J
authors.lastname: Gibson
authors.forename: P Joy
authors.initials: PJ
authors.lastname: Ho
authors.forename: Douglas
authors.initials: D
authors.lastname: Joshua
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D002452:Cell Count; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D016179:Granulocyte Colony-Stimulating Factor
keywords: MDSC; Multiple myeloma; Treg cells; immunotherapy