title: Plasmacytoid dendritic cells induce CD8+ regulatory T cells in human ovarian carcinoma.
abstract: To directly dissect the role of each immune component in human tumor immunopathogenesis, we have studied the interaction between dendritic cells and T cells in the tumor environment of patients with ovarian carcinoma. We previously reported that functional plasmacytoid dendritic cells, but not functionally mature myeloid dendritic cells, accumulated in tumor microenvironments. We now show that tumor ascites macrophage-derived dendritic cells induced tumor-associated antigen-specific CD8+ T cells with effector functions. Strikingly, tumor ascites plasmacytoid dendritic cells induced interleukin-10+ CCR7+ CD45RO+ CD8+ regulatory T cells. Four characteristics have been identified in tumor plasmacytoid dendritic cell-induced CD8+ regulatory T cells: (a) induction of CD8+ regulatory T cells is independent of CD4+ CD25+ T cells; (b) CD8+ regulatory T cells significantly suppress myeloid dendritic cell-mediated tumor-associated antigen-specific T cell effector functions through interleukin-10; (c) repetitive myeloid dendritic cell stimulation can recover CD8+ regulatory T cell-mediated poor T cell proliferation, but not T cell effector function; (d) CD8+ regulatory T cells express functional CCR7, and efficiently migrate with lymphoid homing chemokine MIP-3beta. Primary suppressive CCR7+ CD45RO+ CD8+ T cells are found in the tumor environment of patients with ovarian cancers. Thus, tumor-associated plasmacytoid dendritic cells contribute to the tumor environmental immunosuppressive network. Collectively, tumors manipulate tumor microenvironmental dendritic cell subset distribution and function to subvert tumor immunity. The data are relevant to understanding tumor immunopathology as well as reevaluating tumor immunotherapeutic strategies.
authors.affiliation: Tulane University Health Science Center, New Orleans, Louisiana 70112-2699, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wei
authors.forename: Ilona
authors.initials: I
authors.lastname: Kryczek
authors.forename: Linhua
authors.initials: L
authors.lastname: Zou
authors.forename: Ben
authors.initials: B
authors.lastname: Daniel
authors.forename: Pui
authors.initials: P
authors.lastname: Cheng
authors.forename: Peter
authors.initials: P
authors.lastname: Mottram
authors.forename: Tyler
authors.initials: T
authors.lastname: Curiel
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lange
authors.forename: Weiping
authors.initials: W
authors.lastname: Zou
mesh_terms: D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000276:immunology; D010051:Ovarian Neoplasms / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000276:immunology
chemical_list: C515370:CCR7 protein, human; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D016753:Interleukin-10; D017493:Leukocyte Common Antigens