1. Institute of Immunology, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany
2. Max Delbrück Center for Molecular Medicine, Robert-Roessle Strasse 10, 13122 Berlin, Germany

Correspondence to: Thomas Blankenstein^1,2 Correspondence and requests for materials should be addressed to T.B. (Email: tblanke@mdc-berlin.de).

Abstract

The recognition and elimination of tumours by T cells, a process termed cancer immunosurveillance¹, is effective against certain virus-associated cancers². 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^{3, 4, 5, 6, 7, 8, 9, 10}. The immunosurveillance hypothesis postulates that tumours, if they eventually grow, escaped T-cell recognition by losing immunogenicity^{6, 7, 8}. 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.

1. Institute of Immunology, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany
2. Max Delbrück Center for Molecular Medicine, Robert-Roessle Strasse 10, 13122 Berlin, Germany

Correspondence to: Thomas Blankenstein^1,2 Correspondence and requests for materials should be addressed to T.B. (Email: tblanke@mdc-berlin.de).

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