Demonstration of an interferon γ-dependent tumor surveillance system in immunocompetent mice Journal Article
| Authors: | Kaplan, D. H.; Shankaran, V.; Dighe, A. S.; Stockert, E.; Aguet, M.; Old, L. J.; Schreiber, R. D. |
| Article Title: | Demonstration of an interferon γ-dependent tumor surveillance system in immunocompetent mice |
| Abstract: | This study demonstrates that endogenously produced interferon γ (IFN- γ) 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-γ (i.e., IFN-γ 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-γ-insensitive mice developed tumors more rapidly than wild-type mice when bred onto a background deficient in the p53 tumorsuppressor gene. IFN-γ-insensitive p53(-/-) mice also developed a broader spectrum of tumors compared with mice lacking p53 alone. Using tumor cells derived from methylcholanthrene-treated IFN-γ-insensitive mice, we found IFN-γ'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-γ. Thus, IFN-γ forms the basis of an extrinsic tumor-suppressor mechanism in immunocompetent hosts. |
| Keywords: | signal transduction; human cell; nonhuman; adenocarcinoma; cell proliferation; mouse; animals; mice; lung neoplasms; animal experiment; animal model; tumor cells, cultured; animalia; cancer inhibition; lung adenocarcinoma; gamma interferon; immunogenicity; antigen recognition; neoplasms, experimental; tumor suppressor protein p53; cytokine production; graft rejection; neoplasm transplantation; cytokine release; immunosurveillance; tumor rejection; immunocompetence; mitosis inhibition; tumor escape; interferon type ii; protein sorting signals; methylcholanthrene; 3 methylcholanthrene; humans; human; priority journal; article |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 95 |
| Issue: | 13 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1998-06-23 |
| Start Page: | 7556 |
| End Page: | 7561 |
| Language: | English |
| DOI: | 10.1073/pnas.95.13.7556 |
| PUBMED: | 9636188 |
| PROVIDER: | scopus |
| PMCID: | PMC22681 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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