Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance

Nature. 2005 Sep 1;437(7055):141-6. doi: 10.1038/nature03954.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / genetics
  • Antigens, Polyomavirus Transforming / metabolism
  • Attachment Sites, Microbiological / genetics
  • Epigenesis, Genetic / genetics
  • Immune Tolerance / immunology*
  • Integrases / genetics
  • Integrases / metabolism
  • Interferon-gamma / blood
  • Lac Operon / genetics
  • Mice
  • Mice, Transgenic
  • Neoplasms / blood
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Oncogenes / genetics
  • T-Lymphocytes / immunology*
  • Transforming Growth Factor beta / blood
  • Transforming Growth Factor beta1
  • Viral Proteins / genetics
  • Viral Proteins / metabolism


  • Antigens, Polyomavirus Transforming
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Viral Proteins
  • Interferon-gamma
  • Cre recombinase
  • Integrases