Figure 1. Cryoablation needs to be combined with CTLA-4 blockade to generate systemic immunity of sufficient strength to reject a secondary tumor. (A) A primary TRAMP C2 tumor is inoculated into the left flank of a mouse and allowed to grow until it is large enough to cryoablate. Our model proposes that cryoablation results in the release of antigens, which are taken up by antigen presenting cells (cross-presentation). In the presence of CTLA-4 blockade, SPAS-1 specific T cells maximally proliferate in response to positive signals delivered by the engagement of T cell receptor with SPAS-1 peptide/MHC I complex and CD28 with B7. This enhanced proliferation results in the rejection of a secondary right flank tumor. (B) In the absence of CTLA-4 blockade, CTLA-4 dampens T cell proliferation and a second tumor grows uncontrolled. (C) In absence of cryoablation, diminished antigen cross-presentation results in limited cross-priming of SPAS-1 specific T cells. Even in the presence CTLA-4 blockade, proliferation of SPAS-1 specific T cells is insufficient to mediate rejection of the tumor.