Impact of human bladder cancer cell architecture on autologous T-lymphocyte activation.
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.
Dangles
Virginie
V
Laboratoire d'Immunologie des Tumeurs, ESA 8067 CNRS, Faculté des Sciences Pharmaceutiques et Biologiques de Paris, Université Paris V-René Descartes, Paris, France.
Validire
Pierre
P
Wertheimer
Mireille
M
Richon
Sophie
S
Bovin
Christophe
C
Zeliszewski
Dominique
D
Vallancien
Guy
G
Bellet
Dominique
D
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
D018968:CD58 Antigens; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1