Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development

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

doi:10.1084/jem.20011171

Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development

J Exp Med. 2002 Jan 21;195(2):161-9. doi: 10.1084/jem.20011171.

Authors

Kazuyoshi Takeda¹, Mark J Smyth, Erika Cretney, Yoshihiro Hayakawa, Nobuhiko Kayagaki, Hideo Yagita, Ko Okumura

Affiliation

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

Abstract

Natural killer (NK) cells and interferon (IFN)-gamma 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-gamma-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-gamma. In the absence of TRAIL, NK cells, or IFN-gamma, 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / pharmacology
Apoptosis / genetics
Apoptosis / immunology
Apoptosis Regulatory Proteins
Cytotoxicity, Immunologic / genetics
Cytotoxicity, Immunologic / immunology*
Interferon-gamma / genetics
Interferon-gamma / immunology*
Killer Cells, Natural / immunology*
Male
Membrane Glycoproteins / genetics
Membrane Glycoproteins / immunology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasms, Experimental / genetics
Neoplasms, Experimental / immunology*
Neoplasms, Experimental / prevention & control
TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / immunology*
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / immunology

Substances

Antibodies, Monoclonal
Apoptosis Regulatory Proteins
Membrane Glycoproteins
TNF-Related Apoptosis-Inducing Ligand
Tnfsf10 protein, mouse
Tumor Necrosis Factor-alpha
Tumor Suppressor Protein p53
Interferon-gamma