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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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