Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development.
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.
Takeda
Kazuyoshi
K
Department of Immunology, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan. ktakeda@med.juntendo.ac.jp
Smyth
Mark J
MJ
Cretney
Erika
E
Hayakawa
Yoshihiro
Y
Kayagaki
Nobuhiko
N
Yagita
Hideo
H
Okumura
Ko
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D051017:Apoptosis Regulatory Proteins; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D007371:Interferon-gamma