Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice.

Details

Serval ID
serval:BIB_6AF3862F3C7A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Kaplan D.H., Shankaran V., Dighe A.S., Stockert E., Aguet M., Old L.J., Schreiber R.D.
ISSN
0027-8424 (Print)
ISSN-L
0027-8424
Publication state
Published
Issued date
1998
Volume
95
Number
13
Pages
7556-7561
Language
english
Abstract
This study demonstrates that endogenously produced interferon gamma (IFN-gamma) forms the basis of a tumor surveillance system that controls development of both chemically induced and spontaneously arising tumors in mice. Compared with wild-type mice, mice lacking sensitivity to either IFN-gamma (i.e., IFN-gamma receptor-deficient mice) or all IFN family members (i.e., Stat1-deficient mice) developed tumors more rapidly and with greater frequency when challenged with different doses of the chemical carcinogen methylcholanthrene. In addition, IFN-gamma-insensitive mice developed tumors more rapidly than wild-type mice when bred onto a background deficient in the p53 tumor-suppressor gene. IFN-gamma-insensitive p53(-/-) mice also developed a broader spectrum of tumors compared with mice lacking p53 alone. Using tumor cells derived from methylcholanthrene-treated IFN-gamma-insensitive mice, we found IFN-gamma's actions to be mediated at least partly through its direct effects on the tumor cell leading to enhanced tumor cell immunogenicity. The importance and generality of this system is evidenced by the finding that certain types of human tumors become selectively unresponsive to IFN-gamma. Thus, IFN-gamma forms the basis of an extrinsic tumor-suppressor mechanism in immunocompetent hosts.
Keywords
Adenocarcinoma/immunology, Animals, Graft Rejection/immunology, Humans, Immunocompetence, Interferon-gamma/immunology, Interferon-gamma/physiology, Lung Neoplasms/immunology, Methylcholanthrene, Mice, Neoplasm Transplantation/immunology, Neoplasms, Experimental/chemically induced, Protein Sorting Signals/immunology, Tumor Cells, Cultured, Tumor Escape/immunology, Tumor Suppressor Protein p53/immunology
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:36
Last modification date
20/08/2019 14:25
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