Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance

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Item Type:	Article
Title:	Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance
Creators Name:	Willimsky, G. and Blankenstein, T.
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.
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
Source:	Nature
ISSN:	0028-0836
Publisher:	Nature Publishing Group
Volume:	437
Number:	7055
Page Range:	141-146
Date:	1 September 2005
Official Publication:	https://doi.org/10.1038/nature03954
PubMed:	View item in PubMed

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