Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance.
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.
Willimsky
Gerald
G
Institute of Immunology, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
Blankenstein
Thomas
T
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism; D001287:Attachment Sites, Microbiological / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D007108:Immune Tolerance / Q000276:immunology*; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000097:blood / Q000235:genetics / Q000276:immunology*; D009857:Oncogenes / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000097:blood; D053773:Transforming Growth Factor beta1; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D000952:Antigens, Polyomavirus Transforming; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014764:Viral Proteins; D007371:Interferon-gamma; C045073:Cre recombinase; D019426:Integrases