Necrotic death but not irradiation abolishes costimulation of T-cell effector functions and survival by CD80-expressing tumor cells

Authors

  • Lilian Stärck,

    1. Department of Hematology and Oncology, University Medical Center Charité, Berlin, Germany
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    • The first 2 authors contributed equally to this paper, and share first authorship.

  • Christian Scholz,

    1. Department of Hematology and Oncology, University Medical Center Charité, Berlin, Germany
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    • The first 2 authors contributed equally to this paper, and share first authorship.

  • Thomas Blankenstein,

    1. Max Delbrück Center for Molecular Medicine, Berlin, Germany
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  • Bernd Dörken,

    1. Department of Hematology and Oncology, University Medical Center Charité, Berlin, Germany
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  • Peter T. Daniel

    Corresponding author
    1. Department of Hematology and Oncology, University Medical Center Charité, Berlin, Germany
    • Clinical and Molecular Oncology, Charité, Campus Virchow Klinikum, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany
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    • Fax: +49-30-450-565-956.


Abstract

Tumor vaccination by the use of gene-modified cancer cells that provide costimulatory signals has been successfully applied in preclinical animal models and is currently evaluated in a variety of clinical settings. In previous work, we demonstrated the efficacy of B7.1/CD80 to promote tumor immunity in syngeneic murine models and to prevent deletion of activated T cells by activation-induced cell death (AICD). In clinical trials, tumor cell vaccines are generally inactivated to avoid transfer of live tumor cells, i.e., additional tumor burden. Previous data indicated, however, that inactivation of tumor cells by lethal ionizing irradiation abrogates tumor vaccination by CD80-expressing cells. Here, we compare living and irradiated allogeneic tumor cells regarding their capacity to induce T-cell effector functions and their propensity to interfere with T-cell deletion by apoptosis. Both lethally irradiated and nonirradiated tumor cells facilitated T-cell proliferation, tumor cell lysis, and interfered with T-cell AICD to a similar extent. In contrast, necrotic tumor cells failed to costimulate T-cell effector functions. Thus, irradiation does not seem to hamper tumor cell-mediated costimulation of T-cell effector functions. In contrast, necrosis of gene-modified tumor cells abrogates costimulation of T cells by CD80-expressing cells. © 2005 Wiley-Liss, Inc.

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