title: Circulating and tumor-infiltrating myeloid cell subsets in patients with bladder cancer.
abstract: Both cancer-related inflammation and tumor-induced immune suppression are associated with expansion of myeloid cell subsets including myeloid-derived suppressor cells. However, little known regarding characteristics of myeloid cells in patients with bladder cancer. In this study, we analyzed myeloid cells from peripheral blood (PBMC) and tumor tissue that were collected from patients with superficial noninvasive and invasive urothelial carcinomas. Our results demonstrate that PBMC from bladder cancer patients contain two major CD11b myeloid cell subsets: granulocyte-type CD15(high)  CD33(low)  cells and monocyte-type CD15(low)  CD33(high)  cells. The number of circulating granulocytic but not monocytic myeloid cells in cancer patients was markedly increased when compared to healthy individuals. Both myeloid cell subsets from cancer patients were highly activated and produced substantial amounts of proinflammatory chemokines/cytokines including CCL2, CCL3, CCL4, G-CSF, IL-8 and IL-6. Granulocytic myeloid cells were able to inhibit in vitro T cell proliferation through induction of CD4(+) Foxp3(+)  T regulatory cells. Analysis of bladder cancer tissues revealed that tumors were infiltrated with monocyte-macrophage CD11b(+) HLA-DR(+)  and granulocytic CD11b(+) CD15(+) HLA-DR(-)  myeloid cells. Collectively, this study identifies myeloid cell subsets in patients with bladder cancer. We demonstrate that these highly activated inflammatory myeloid cells represent a source of multiple chemokines/cytokines and may contribute to inflammation and immune dysfunction in bladder cancer.
authors.affiliation: Department of Urology, University of Florida, College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Evgeniy
authors.initials: E
authors.lastname: Eruslanov
authors.forename: Molly
authors.initials: M
authors.lastname: Neuberger
authors.forename: Irina
authors.initials: I
authors.lastname: Daurkin
authors.forename: George Q
authors.initials: GQ
authors.lastname: Perrin
authors.forename: Chester
authors.initials: C
authors.lastname: Algood
authors.forename: Philipp
authors.initials: P
authors.lastname: Dahm
authors.forename: Charles
authors.initials: C
authors.lastname: Rosser
authors.forename: Johannes
authors.initials: J
authors.lastname: Vieweg
authors.forename: Scott M
authors.initials: SM
authors.lastname: Gilbert
authors.forename: Sergei
authors.initials: S
authors.lastname: Kusmartsev
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018845:CD11 Antigens / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D016256:Lewis X Antigen / Q000378:metabolism; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology*; D063268:Sialic Acid Binding Ig-like Lectin 3; D001749:Urinary Bladder Neoplasms / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018845:CD11 Antigens; C571163:CD33 protein, human; D016207:Cytokines; D016256:Lewis X Antigen; D063268:Sialic Acid Binding Ig-like Lectin 3