title: Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity.
abstract: Suppression of dendritic cell function in cancer patients is thought to contribute to the inhibition of immune responses and disease progression. Molecular mechanisms of this suppression remain elusive, however. Here, we show that a fraction of blood monocyte-derived myeloid dendritic cells (MDCs) express B7-H1, a member of the B7 family, on the cell surface. B7-H1 could be further upregulated by tumor environmental factors. Consistent with this finding, virtually all MDCs isolated from the tissues or draining lymph nodes of ovarian carcinomas express B7-H1. Blockade of B7-H1 enhanced MDC-mediated T-cell activation and was accompanied by downregulation of T-cell interleukin (IL)-10 and upregulation of IL-2 and interferon (IFN)-gamma. T cells conditioned with the B7-H1-blocked MDCs had a more potent ability to inhibit autologous human ovarian carcinoma growth in non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. Therefore, upregulation of B7-H1 on MDCs in the tumor microenvironment downregulates T-cell immunity. Blockade of B7-H1 represents one approach for cancer immunotherapy.
authors.affiliation: Tulane University Health Science Center, New Orleans, Louisiana, USA.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Curiel
authors.forename: Shuang
authors.initials: S
authors.lastname: Wei
authors.forename: Haidong
authors.initials: H
authors.lastname: Dong
authors.forename: Xavier
authors.initials: X
authors.lastname: Alvarez
authors.forename: Pui
authors.initials: P
authors.lastname: Cheng
authors.forename: Peter
authors.initials: P
authors.lastname: Mottram
authors.forename: Roman
authors.initials: R
authors.lastname: Krzysiek
authors.forename: Keith L
authors.initials: KL
authors.lastname: Knutson
authors.forename: Ben
authors.initials: B
authors.lastname: Daniel
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Zimmermann
authors.forename: Odile
authors.initials: O
authors.lastname: David
authors.forename: Matthew
authors.initials: M
authors.lastname: Burow
authors.forename: Alan
authors.initials: A
authors.lastname: Gordon
authors.forename: Nina
authors.initials: N
authors.lastname: Dhurandhar
authors.forename: Leann
authors.initials: L
authors.lastname: Myers
authors.forename: Ruth
authors.initials: R
authors.lastname: Berggren
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Alvarez
authors.forename: Dominique
authors.initials: D
authors.lastname: Emilie
authors.forename: David T
authors.initials: DT
authors.lastname: Curiel
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Weiping
authors.initials: W
authors.lastname: Zou
mesh_terms: D000818:Animals; D015703:Antigens, CD; D018122:B7-1 Antigen / Q000502:physiology*; D060890:B7-H1 Antigen; D001798:Blood Proteins; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D022423:Myeloid Cells / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D010455:Peptides; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C423236:CD274 protein, human; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; D010455:Peptides; D016753:Interleukin-10; D018664:Interleukin-12