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Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance

Official URL:https://doi.org/10.1038/nature03954
PubMed:View item in PubMed
Creators Name:Willimsky, G. and Blankenstein, T.
Journal Title:Nature
Journal Abbreviation:Nature
Volume:437
Number:7055
Page Range:141-146
Date:1 September 2005
Keywords:Genetic Epigenesis, Immune Tolerance, Integrases, Interferon Type II, Lac Operon, Microbiological Attachment Sites, Neoplasms, Oncogenes, Polyomavirus Transforming Antigens, Transgenic Mice, T-Lymphocytes, Transforming Growth Factor beta, Transforming Growth Factor beta1, Viral Proteins, Animals, Mice
Abstract:The recognition and elimination of tumours by T cells, a process termed cancer immunosurveillance, is effective against certain virus-associated cancers. Spontaneous tumours often induce a specific immune response and are therefore also immunogenic. However, it is not clear whether they can be controlled by T cells. The immunosurveillance hypothesis postulates that tumours, if they eventually grow, escaped T-cell recognition by losing immunogenicity. Here we show, by generating a mouse model of sporadic cancer based on rare spontaneous activation of a dormant oncogene, that immunogenic tumours do not escape their recognition but induce tolerance. In this model, tumours derive from single cells and express a tumour-specific transplantation rejection antigen. Whereas vaccinated mice remain tumour-free throughout their lifetime, naive mice always develop a progressively growing tumour. We also show that despite specific recognition by T cells, the tumours do not lose their intrinsic immunogenicity and are rejected after transplantation in T-cell-competent recipients. Furthermore, in the primary host tumour-induced tolerance is associated with the expansion of non-functional T cells. Together, our data argue against immunosurveillance of spontaneous cancer.
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Item Type:Article

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