Radiofrequency ablation combined with immunotherapy to treat hepatocellular carcinoma: a comprehensive review

Sep 23, 2026

Hepatocellular carcinoma (HCC) is a highly immunogenic tumor and a leading global cause of cancer-related deaths, with rising incidence. A systematic review evaluates combining immunotherapy with radiofrequency ablation (RFA) as an emerging strategy. Searches in PubMed and Web of Science collect studies on RFA and immunotherapy for HCC, followed by mechanistic analysis and assessment of safety and effectiveness. Evidence indicates synergistic enhancement of antitumor immunity, improved immune microenvironment reconstruction, and reduced recurrence risk while maintaining controllable safety.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Background and aim

Methods

Results

Conclusions

Background

Epidemiology and clinical staging

Standard treatments and the role of RFA

Xie etal. BMC Surgery (2025) 25:47 [https://doi.org/10.1186/s12893-025-02778-z](https://doi.org/10.1186/s12893-025-02778-z) BMC Surgery REVIEW Open Access Radiofrequency ablation combined with immunotherapy to treat hepatocellular carcinoma: a comprehensive review Gui-Lin Xie 1†, Zhi-Han Zhong2,3†, Tai-Wei Ye2,3* and Zun-Qiang Xiao2* Abstract Background and aim Hepatocellular carcinoma (HCC) is a highly immunogenic tumor and the third leading cause of cancer-related deaths worldwide with an increasing incidence. Therefore, the combination of immunotherapy with other approaches, such as anti-angiogenic agents and local area therapy, has become a new strategy for HCC treatment. Methods We searched PubMed and Web of Science and extracted publications relating to the radiofrequency ablation (RFA) and immunotherapy. The search terms were: “radiofrequency ablation”,“immunotherapy” and“hepatocellular carcinoma”, and manual searches of eligible articles from literature reference lists were performed. We then thoroughly reviewed the literature on ablation combined with immunotherapy for HCC, analyzed the relevant mechanism, and explored the safety and effectiveness of this form of combination therapy. Results RFA combined with immunotherapy in HCC is reported to have good efficacy and controllable safety. On the one hand, RFA can induce the immunogenic substances including Ficolin-3, IL-1 and heat shock protein and regulate the immune cells by mediating the Th1/Th2 ratio, increasing Th17 cells, etc. On the other hand, RFA treatment can lead to tumor immune microenvironment reconstruction, increasing the proportion of functional T cells and upregulate PD-1 inT cells in distant tumors without RFA. This combined strategy has the ability to enhance the antitumor immune response through synergies, significantly reduce the risk of recurrence and improve survival. Conclusions RFA combined with immunotherapy yields a good synergistic effect: it can further strengthen antitumor response, delay distant tumor growth, reduce tumor recurrence and metastasis, providing new options for HCC systemic treatment. Keywords Hepatocellular carcinoma, Radiofrequency ablation, Immunotherapy, Combination therapy †Gui-Lin Xie and Zhi-Han Zhong contributed equally to this work. *Correspondence: Tai-Wei Ye [ytaiweisur@163.com](ytaiweisur@163.com)[ ](ytaiweisur@163.com)Zun-Qiang Xiao [zqxiao@zcmu.edu.cn](zqxiao@zcmu.edu.cn) 1Department of Hepatobiliary Surgery, Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang, China 2General Surgery, Cancer Center, Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Affiliated People’s Hospital, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang, China 3The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/l](vecommons.org/l)icenses/by-nc-nd/4.0/. Xi

FAQs

Why is combining immunotherapy with radiofrequency ablation considered for HCC treatment?

HCC is highly immunogenic, and combining immunotherapy with local approaches like RFA is presented as a new strategy to improve outcomes. The review targets both efficacy and controllable safety.

How does radiofrequency ablation potentially enhance immunotherapy effects?

RFA can induce immunogenic substances such as Ficolin-3, IL-1, and heat shock proteins, and it may regulate immune cell balance via Th1/Th2 modulation and increased Th17 cells. It can also reconstruct the tumor immune microenvironment and increase functional T cells while upregulating PD-1 in distant tumor sites without RFA.

What overall treatment benefits are reported for the RFA plus immunotherapy combination?

The combined strategy is reported to have good efficacy and controllable safety, strengthen antitumor immune response, delay distant tumor growth, and reduce tumor recurrence and metastasis, potentially improving survival.

Sep 23, 2026

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