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

• Published in: Cardiovascular and interventional radiology Vol. 43; no. 9; pp. 1353 - 1361
• Main Authors: Zhang, Liang, Wang, Jun, Jiang, Jinhua, Zhang, Mingming, Shen, Jialin
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2020; Springer Nature B.V
• Subjects: Ablation; Animals; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - surgery; Cardiology; Catheter Ablation - methods; CD4 antigen; CTLA-4 Antigen - antagonists & inhibitors; CTLA-4 protein; Disease control; Disease Progression; Growth rate; Hepatocellular carcinoma; Hepatoma; Imaging; Immune Checkpoint Inhibitors - therapeutic use; Laboratory Investigation; Liver cancer; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Liver Neoplasms - surgery; Lymphocytes; Male; Medicine; Medicine & Public Health; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Nuclear Medicine; Postoperative Period; Radiofrequency ablation; Radiology; Tumor cells; Tumors; Ultrasound; γ-Interferon; Local tumor progression; Radiofrequency ablation; Residual tumor; Hepatocellular carcinoma; Anti-CTLA-4 therapy; Anti-tumor immunity
• DOI: 10.1007/s00270-020-02505-6
• ISSN: 0174-1551; 1432-086X

Purpose 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. Materials and Methods 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. Results 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. Conclusions 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.