In vivo blockade of CTLA-4 enhances the priming of responsive T cells but fails to prevent the induction of tumor antigen-specific tolerance

The efficacy of therapeutic vaccination for the treatment of cancer is limi ted by peripheral tolerance to tumor antigens. In vivo blockade of CTLA-4, a negative regulator of T cell function, can induce the regression of estab lished tumors and can augment the tumor rejection achieved through therapeu tic vaccination. These outcomes may reflect enhanced tumor-specific T cell priming and/or interference with the development of tolerance to tumor anti gens, We examined the effect of CTLA-4 blockade on the fate and function of T cells specific for a model tumor antigen in the tumor-bearing host. We f ound that while CTLA-4 blockade enhanced the priming of responsive T cells, it did not prevent the induction of tolerance to tumor antigens, These res ults demonstrate that there is a critical window in which the combination o f CTLA-4 blockade and vaccination achieves an optimal response, and they po int to mechanisms other than CTLA-4 engagement in mediating peripheral T ce ll tolerance to tumor antigens.