CTLA-4 blockade synergizes with cryoablation to mediate tumor rejection - PubMed (original) (raw)

CTLA-4 blockade synergizes with cryoablation to mediate tumor rejection

Rebecca Waitz et al. Oncoimmunology. 2012.

Abstract

We report that cryoablation of primary tumors synergizes with anti-CTLA-4 treatment to mediate rejection of secondary tumors in the TRAMP mouse model of prostate cancer. T cells, in particular CD8(+) T cells specific for the TRAMP antigen SPAS-1, were enriched in both secondary tumors and spleens of combination-treated mice.

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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.

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