title: Myeloid-derived suppressor cells in the peripheral blood of cancer patients contain a subset of immature neutrophils with impaired migratory properties.
abstract: In tumor-bearing mice, immunosuppressive granulocytic and monocytic MDSC have been identified. The identity and function of MDSC in cancer patients are less clear and need further characterization. We analyzed the peripheral blood of 103 patients with HNC, lung cancer, or cancers of bladder and ureter. Based on sedimentation properties in density gradients, a subset of LD-PMN was identified and analyzed. LD-PMN were expanded in the peripheral blood of cancer patients, suppressed proliferation, and IFN-γ production of polyclonally stimulated T cells and thus, qualify as human MDSC. Immunophenotyping and morphological analysis revealed the accumulation of immature PMN in the MDSC fraction. Neutrophilic MDSC showed altered surface marker expression, prolonged survival, and impaired effector functions when compared with conventional, mature PMN of regular density. MDSC displayed markedly reduced chemotaxis toward tumor-conditioned medium and lacked expression of chemokine receptors CXCR1 and CXCR2, which are normally required for PMN extravasation from the bloodstream and subsequent tissue infiltration. Collectively, our data suggest the accumulation and persistence of long-lived, immature granulocytic MDSC with T cell-suppressive function and impaired migratory properties in the peripheral blood of cancer patients.
authors.affiliation: Department of Otorhinolaryngology and Urology, University Hospital Essen, Essen, Germany. sven.brandau@uk-essen.de
authors.forename: Sven
authors.initials: S
authors.lastname: Brandau
authors.forename: Sokratis
authors.initials: S
authors.lastname: Trellakis
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bruderek
authors.forename: Dominik
authors.initials: D
authors.lastname: Schmaltz
authors.forename: Gabriele
authors.initials: G
authors.lastname: Steller
authors.forename: Motaz
authors.initials: M
authors.lastname: Elian
authors.forename: Henrik
authors.initials: H
authors.lastname: Suttmann
authors.forename: Marcus
authors.initials: M
authors.lastname: Schenck
authors.forename: Jürgen
authors.initials: J
authors.lastname: Welling
authors.forename: Peter
authors.initials: P
authors.lastname: Zabel
authors.forename: Stephan
authors.initials: S
authors.lastname: Lang
mesh_terms: D017209:Apoptosis / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000473:pathology*; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology; D008297:Male; D023461:Myeloid Progenitor Cells / Q000276:immunology* / Q000473:pathology*; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology*; D014407:Tumor Cells, Cultured