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‐γ), 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. © 2001 Wiley‐Liss, Inc.