Liang Zhang1, Jun Wang1, Jinhua Jiang1, Mingming Zhang2, Jialin Shen3. 1. Department of Oncology Interventional Therapy, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pujian Road, Pudong, Shanghai, 200127, People's Republic of China. 2. Department of Clinical Medicine, Jining Medical College, No. 16 Hehua Street, Jining, Shandong, People's Republic of China. 3. Department of Oncology Interventional Therapy, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pujian Road, Pudong, Shanghai, 200127, People's Republic of China. jialinshen123@163.com.
Abstract
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.
PURPOSE: To evaluate whether anti-CTLA-4 therapy could suppress residual tumor progression and improve survival after insufficient radiofrequency ablation (RFA) in a subcutaneous murinehepatocellular 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 H22tumor 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.
Authors: Renske J E van den Bijgaart; Fabian Schuurmans; Jurgen J Fütterer; Marcel Verheij; Lenneke A M Cornelissen; Gosse J Adema Journal: Front Immunol Date: 2021-04-14 Impact factor: 7.561