CTLA-4 Blockade Suppresses Progression of Residual Tumors and Improves Survival After Insufficient Radiofrequency Ablation in a Subcutaneous Murine Hepatoma Model.

Abstract

To evaluate whether anti-CTLA-4 therapy could suppress residual tumor progression and improve survival after insufficient radiofrequency ablation (RFA) in a subcutaneous murine hepatocellular carcinoma (HCC) model. Forty mice with tumors established on their right flanks were randomly divided into four groups: control group (no treatment), RFA group (insufficient RFA alone), anti-CTLA-4 group (anti-CTLA-4 monotherapy), and RFA + anti-CTLA-4 group (insufficient RFA + anti-CTLA-4). In each group, eight mice were assessed for residual tumors and survival; another two mice were killed on day 14 for histopathologic studies. On day 42, a re-challenge test was performed in the survived mice of RFA + anti-CTLA-4 group to determine whether systemic anti-tumor immunity was established. The specific growth rate of residual tumors was significantly less in RFA + anti-CTLA-4 group than that of the other three groups (all p < 0.05). The disease control rate was 50% in RFA + anti-CTLA-4 group, while no animals in the other three groups showed disease control. Animals in RFA + anti-CTLA-4 group had longer survival times than those in the other three groups (all p < 0.05). Expression of CD4+ lymphocytes in residual tumors and IFN-γ production in response to H22 tumor cells were significantly higher in RFA + anti-CTLA-4 group than those in the other three groups (all p < 0.05). Three of the five survived mice in RFA + anti-CTLA-4 group underwent tumor re-challenge exhibited tumor rejection. The present study demonstrated that CTLA-4 blockade injection could suppress the growth of residual tumors and improve survival after insufficient RFA in a subcutaneous murine HCC model.