Antitumor Immunity Augmented by Combining Radiofrequency Ablation with Anti–CTLA-4 Therapy in a Subcutaneous Murine Hepatoma Model

Abstract

PurposeTo evaluate whether antitumor immunity is enhanced by combining radiofrequency (RF) ablation and anti-cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) therapy and to evaluate its effect on untreated tumors. Materials and MethodsFirst, 40 mice with tumors established in the bilateral flanks were randomly divided into 4 groups: the control group, the RF ablation-alone group, the anti-CTLA-4-alone group, and the RF ablation + anti-CTLA-4 group. In each group, 8 mice were used for untreated tumor evaluation and survival observation, and another 2 mice were killed for histopathologic study. Then, a rechallenge test was performed in another 32 mice to determine whether systemic antitumor immunity was established. ResultsAlthough the volume of the untreated tumors continued to increase until the end of the observation in all groups, tumor growth rates in the RF ablation + anti-CTLA-4 group were significantly smaller than tumor growth rates in the other 3 groups (all P < .05). The overall survival time of mice in the RF ablation + anti-CTLA-4 group was significantly longer than that of mice in the other 3 groups (all P < .05). Histopathologic studies of the untreated tumors showed more CD4-and CD8+ lymphocyte infiltration in mice from the RF ablation + anti-CTLA-4 group than in mice from the other 3 groups (all P < .05). After a tumor rechallenge, tumor rejection was apparent in 75% of the mice in the RF ablation + anti-CTLA-4 group, in 25% of the mice in the RF ablation group, and in 0% of the mice in the control and anti-CTLA-4 groups. ConclusionsThis study demonstrated that RF ablation-induced systemic antitumor immunity was enhanced by the combined use of anti-CTLA-4 therapy in a multi-subcutaneous murine hepatoma model.