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PMID: 11805143 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of experimental medicine ·Vol. 195 ·No. 2 ·2002-01-21 ·Pages 161-9

Takeda K, Smyth MJ, Cretney E, Hayakawa Y, Kayagaki N, Yagita H, Okumura K

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.

MeSH Terms
Animals Antibodies, Monoclonal/immunology,pharmacology Apoptosis/genetics,immunology Apoptosis Regulatory Proteins Cytotoxicity, Immunologic/genetics,immunology Interferon-gamma/genetics,immunology Killer Cells, Natural/immunology Male Membrane Glycoproteins/genetics,immunology Mice Mice, Inbred C57BL Mice, Knockout Neoplasms, Experimental/genetics,immunology,prevention & control TNF-Related Apoptosis-Inducing Ligand Tumor Necrosis Factor-alpha/genetics,immunology Tumor Suppressor Protein p53/genetics,immunology
Chemicals
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
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Takeda Kazuyoshi
Department of Immunology, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan. ktakeda@med.juntendo.ac.jp
Smyth Mark J
Cretney Erika
Hayakawa Yoshihiro
Kayagaki Nobuhiko
Yagita Hideo
Okumura Ko
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20011171
Email
ktakeda@med.juntendo.ac.jp
Published
2002-01-21
Pages
161-9
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193611
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20011171 PMC Full Text View journal details
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