[Opportunities and defiance of therapeutic anti-tumoral vaccination]

Therapeutic anti-cancer vaccines containing tumor-specific antigens recognized by T lymphocytes are thought to stimulate high numbers of anti-vaccine cytolytic T lymphocytes (CTL) which then can lyse the tumor cells. To understand why these vaccines are followed by tumor regressions in only 10% of the patients, we analysed the tumor-specific immune responses of these patients. Contrary to our expectations, the anti-vaccine CTL responses were of very low level. However, regressing tumors were massively infiltrated by anti-tumor T cells of other specificities, including new anti-tumor CTL clonotypes that emerged following vaccination. We now believe that the role of the anti-vaccine CTL is to activate or restimulate large numbers of other anti-tumor CTL. Their ability to initiate this response is probably more important than their number. These results have important consequences for the improvement of the clinical efficacy of anti-cancer vaccines.