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

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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.

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Funding

This study was funded by Shanghai Anticancer Association EYAS PROJECT (Grant Number SACA-CY1C17).

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Author notes

  1. Drs. Liang Zhang and Jun Wang contributed equally to this work, they are joint first authors.

Authors and Affiliations

  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

    Liang Zhang, Jun Wang, Jinhua Jiang & Jialin Shen

  2. Department of Clinical Medicine, Jining Medical College, No. 16 Hehua Street, Jining, Shandong, People’s Republic of China

    Mingming Zhang

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  1. Liang Zhang
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  2. Jun Wang
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  3. Jinhua Jiang
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Correspondence to Jialin Shen.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Zhang, L., Wang, J., Jiang, J. et al. CTLA-4 Blockade Suppresses Progression of Residual Tumors and Improves Survival After Insufficient Radiofrequency Ablation in a Subcutaneous Murine Hepatoma Model. Cardiovasc Intervent Radiol 43, 1353–1361 (2020). https://doi.org/10.1007/s00270-020-02505-6

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  • DOI: https://doi.org/10.1007/s00270-020-02505-6

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