Augmentation of Checkpoint Inhibitor Tumor Response via Adjuvant Cryoablation in Murine Lung, Breast and Colon Cancer Models

Abstract

Purpose: Focal cryoablation for cancer is an immunogenic process that can also result in a global antitumor response. We hypothesize that combining cryoablation with immunotherapy will yield an augmented synergistic antitumor response in syngenic murine tumor models. Methods: Mice were implanted with bilateral flank tumors of lung, breast or colon cancer and were treated with checkpoint inhibitor therapy (anti-PD-1/anti-CTLA-4) and/or unilateral cryoablation. Tumor volumes were measured for up to 4 weeks to track growth delay, and survival analysis was performed with an endpoint of tumor volume >750mm3. Results: The lung cancer model did not demonstrate growth delay or survival benefit to immunotherapy, cryoablation, or both compared to vehicle. The colon cancer model was sensitive to immunotherapy regimens, with both groups demonstrating growth delay and improved survival; the addition of cryoablation to immunotherapy resulted in improved survival compared to immunotherapy alone, as well as complete tumor regression in 80% of cases. The breast cancer model was partially responsive to immunotherapy, which resulted in a growth delay and improved survival; again this response was improved by cryoablation over immunotherapy alone, however no complete tumor regression was observed. Conclusions: Checkpoint inhibitors are a potent yet cancer type-dependent therapy. The antitumor immune response can be augmented by the combination of immunotherapy with focal cryoablation.