title: Impact of human bladder cancer cell architecture on autologous T-lymphocyte activation.
abstract: To investigate the influence of tumor cell architecture on T-cell activation, we used an autologous human model based on 2 bladder tumor cell lines as targets for cytotoxic tumor-infiltrating lymphocytes (TILs). These tumor cell lines were grown in vitro as either standard 2-dimensional (2D) monolayers or 3-dimensional (3D) spheroids. T-cell activation was determined by measuring the production of three major cytokines (tumor necrosis factor, granulocyte/macrophage colony-stimulating factor and interferon-gamma), known to be secreted by most activated TILs. Changes in the architecture of target cells from 2D to 3D induced a dramatic decrease in their capacity for stimulating TILs. Interestingly, neither TIL infiltration nor MHC class I, B7.1 costimulatory or lymphocyte function-associated factor-3 adhesion molecule downregulation played a major role in this decrease. These findings demonstrate that tumor architecture has a major impact on T-cell activation and might be implicated in the escape of tumor cells from the immune system.
authors.affiliation: Laboratoire d'Immunologie des Tumeurs, ESA 8067 CNRS, Faculté des Sciences Pharmaceutiques et Biologiques de Paris, Université Paris V-René Descartes, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Dangles
authors.forename: Pierre
authors.initials: P
authors.lastname: Validire
authors.forename: Mireille
authors.initials: M
authors.lastname: Wertheimer
authors.forename: Sophie
authors.initials: S
authors.lastname: Richon
authors.forename: Christophe
authors.initials: C
authors.lastname: Bovin
authors.forename: Dominique
authors.initials: D
authors.lastname: Zeliszewski
authors.forename: Guy
authors.initials: G
authors.lastname: Vallancien
authors.forename: Dominique
authors.initials: D
authors.lastname: Bellet
mesh_terms: D018968:CD58 Antigens / Q000032:analysis; D016207:Cytokines / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D018874:Spheroids, Cellular; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000473:pathology
chemical_list: D018968:CD58 Antigens; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1