Tumor-specific immunotherapy based on dominant models of natural tolerance

The assumption that cancer immunotherapy may be based on the existence of autoreactive lymphocytes recognizing self-antigens on cancer cells, obviously opens a new opportunity. Nevertheless this analysis, relying on a recessive model of natural tolerance, limits the approach to try to activate peripheral lymphocytes, by increasing costimulatory signals or using modified self-antigens for immunization. Here we hypothesize that, based on emerging dominant tolerance notions in autoimmunity, it would be possible to induce a specific autoimmunity against tumor cells and arrest their growth following the removal of regulatory T cells. These immunoregulatory cells suppress available immunocompetent autoreactive cells capable of destroying tumor cells. Therefore, in order to reach a complete tumor-specific autoimmunity it is necessary to combine the T cell immunosuppression which abrogates the regulatory cells, with the cancer vaccines, which induces extensive proliferation of lymphoid cells directed towards specificities on tumor cells. (C) 2000 Harcourt Publishers Ltd.