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Potential of Radiofrequency Ablation in Combination with Immunotherapy in the Treatment of Hepatocellular Carcinoma

Guangfu Li, Kevin F Staveley-O’Carroll and Eric T Kimchi

Radiofrequency ablation (RFA) is an important treatment option for patients with early hepatocellular carcinoma (HCC). RFA offers a reliable, reproducible modality to effectively treat hepatic lesions with minimal collateral damage to the surrounding hepatic parenchyma. In addition to traditional open operative techniques, RFA can be performed percutaneously or laparoscopically to minimize the physiologic insult to the patient. Due to the concomitant hepatic damage and dysfunction that often is present in patients with HCC these factors make RFA a frequently utilized therapeutic option. However, RFA is most efficacious in treating smaller tumors (≤ 2 cm), particularly when an ablation margin of ≥ 4-5 mm can be obtained. RFA has diminishing utility in larger tumors, resulting in reduced three and five year overall survival rates when compared to surgical resection. Multimodal approaches to include RFA with other standard and investigational approaches have become a subject of recent interest. RFA capably produces cellular destruction causing liberation of a substantial amount of antigens, many of which are tumor-specific providing a favorable environment for immune recognition. We propose that utilizing an immunotherapeutic approach in conjunction with RFA is the next logical step in the treatment of HCC. In this review, we summarize how RFA modulates antitumor immunity and works in concert with immunotherapy in the treatment of HCC. The information provided is expected to help the future design of novel RFA-integrated immunotherapies which are able to generate durable and powerful antitumor immune response to achieve optimal tumor control.