Expression of the ULBP ligands for NKG2D by B-NHL cells plays an important role in determining their susceptibility to rituximab-induced ADCC

Authors

  • Atsushi Inagaki,

    1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
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  • Takashi Ishida,

    Corresponding author
    1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
    • Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan
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    • Fax: +81-52-852-0849.

  • Hiroki Yano,

    1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
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  • Toshihiko Ishii,

    1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
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  • Shigeru Kusumoto,

    1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
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  • Asahi Ito,

    1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
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  • Masaki Ri,

    1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
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  • Fumiko Mori,

    1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
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  • Jianmin Ding,

    1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
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  • Hirokazu Komatsu,

    1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
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  • Shinsuke Iida,

    1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
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  • Ryuzo Ueda

    1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
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Abstract

Antibody-dependent cellular cytotoxicity (ADCC) is a major antitumor mechanism of action of therapeutic monoclonal antibodies (mAbs). The aim of this study was to identify tumor-associated factors which determine susceptibility to rituximab-induced ADCC. Thirty different CD20+ non-Hodgkin lymphoma cell lines were phenotyped for characteristics such as level of expression of NKG2D ligands, and the influence thereof on susceptibility to rituximab-induced ADCC was established. The present study demonstrated that tumor cell susceptibility to rituximab-induced ADCC was determined by 3 major tumor-associated factors: (i) the amount of the target molecule, CD20; (ii) the amount of the ligands for inhibitory killer Ig-like receptors, major histocompatibility complex class I; and (iii) the amounts of some of the NKG2D ligands, especially UL16-binding protein (ULBP) 1–3. The importance of the ULBPs was confirmed using antibody blockade. In conclusion, this is the first report to show the importance for rituximab-induced ADCC of ULBPs expressed on tumor cells. The ULBPs could be valuable diagnostic biological markers and significant targets for immunotherapy to improve efficacy not only of rituximab but also of other therapeutic mAbs. © 2009 UICC

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