Tumor-specific immunotherapy based on dominant models of natural tolerance

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