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

Author:

Takeda Kazuyoshi1,Smyth Mark J.2,Cretney Erika2,Hayakawa Yoshihiro3,Kayagaki Nobuhiko1,Yagita Hideo1,Okumura Ko1

Affiliation:

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

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

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

Abstract

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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