Critical Role for Tumor Necrosis Factor–related Apoptosis-inducing Ligand in Immune Surveillance Against Tumor Development

Takeda , Kazuyoshi; Smyth , Mark J.; Cretney , Erika; Hayakawa , Yoshihiro; Kayagaki , Nobuhiko; Yagita , Hideo; Okumura , Ko

doi:10.1084/jem.20011171

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Article| January 14 2002

Critical Role for Tumor Necrosis Factor–related Apoptosis-inducing Ligand in Immune Surveillance Against Tumor Development

Kazuyoshi Takeda,

Kazuyoshi Takeda

1Department of Immunology, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan

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Mark J. Smyth,

Mark J. Smyth

2Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 3002, Australia

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Erika Cretney,

Erika Cretney

2Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 3002, Australia

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Yoshihiro Hayakawa,

Yoshihiro Hayakawa

3Department of Pathogenic Biochemistry, Research Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan

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Nobuhiko Kayagaki,

Nobuhiko Kayagaki

1Department of Immunology, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan

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Hideo Yagita,

Hideo Yagita

1Department of Immunology, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan

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Ko Okumura

1Department of Immunology, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan

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Author and Article Information

Kazuyoshi Takeda

1Department of Immunology, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan

Mark J. Smyth

2Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 3002, Australia

Erika Cretney

2Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 3002, Australia

Yoshihiro Hayakawa

3Department of Pathogenic Biochemistry, Research Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan

Nobuhiko Kayagaki

1Department of Immunology, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan

Hideo Yagita

1Department of Immunology, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan

Ko Okumura

1Department of Immunology, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan

Address correspondence to Kazuyoshi Takeda, Dept. of Immunology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Phone: 81-3-3818-9284; Fax: 81-3-3813-0421; E-mail: [email protected]

*

Abbreviations used in this paper: ASGM1, asialo GM1; MCA, methylcholanthrene; TRAIL, TNF-related apoptosis-inducing ligand.

Received: July 05 2001

Revision Received: November 12 2001

Accepted: November 28 2001

Online ISSN: 1540-9538

Print ISSN: 0022-1007

The Rockefeller University Press

2002

J Exp Med (2002) 195 (2): 161–169.

https://doi.org/10.1084/jem.20011171

Natural killer (NK) cells and interferon (IFN)-γ have been implicated in immune surveillance against tumor development. Here we show that tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) plays a critical role in the NK cell–mediated and IFN-γ–dependent tumor surveillance. Administration of neutralizing monoclonal antibody against TRAIL promoted tumor development in mice subcutaneously inoculated with a chemical carcinogen methylcholanthrene (MCA). This protective effect of TRAIL was at least partly mediated by NK cells and totally dependent on IFN-γ. In the absence of TRAIL, NK cells, or IFN-γ, TRAIL-sensitive sarcomas preferentially emerged in MCA-inoculated mice. Moreover, development of spontaneous tumors in p53^+/− mice was also promoted by neutralization of TRAIL. These results indicated a substantial role of TRAIL as an effector molecule that eliminates developing tumors.

The Rockefeller University Press

2002

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