RFA and anti-PD-1 combination therapy suppresses abscopal HCC tumors and prevents recurrence in mice
Published 16 July, 2025
Hepatocellular carcinoma (HCC), the most prevalent form of primary liver cancer, remains a leading cause of cancer-related mortality worldwide. Although radiofrequency ablation (RFA) is the first-line curative treatment, its efficacy is limited by the immunosuppressive tumor microenvironment. This therapeutic gap underscores the crucial need for adjuvant therapies to enhance anti-tumor immunity and augment RFA’s abscopal effects.
Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have improved cancer treatment by rescuing exhausted T-cells and restoring anti-tumor immunity. With this knowledge, combining RFA with anti-PD-1 therapy has been widely explored as a promising strategy to enhance the abscopal effect and improve survival in an HCC mouse model.
In a study published in the KeAi Liver Research, researchers at the First Affiliated Hospital of Sun Yat-sen University demonstrated that combining RFA with anti-PD-1 therapy significantly suppressed the growth of non-ablated distant tumors and prolonged survival in HCC-bearing mice. This treatment remodeled the immune microenvironment of abscopal tumors, characterized by increased infiltration of CD8+ T cells and dendritic cells alongside reduced PMN-MDSCs, mechanistically involving JAK-STAT activation and CXCL10-mediated chemotaxis.
“Using a bilateral subcutaneous HCC mouse model, we found that the RFA + anti-PD-1 combination induces long-lasting immune memory and prevents tumor recurrence,” shares corresponding author Xuezhen Zeng. “This dual-action mechanism provides evidence for advancing this strategy into clinical trials for HCC patients with a high risk of recurrence.”
In particular, RFA + anti-PD-1 therapy simultaneously treats tumors and prevents recurrence through durable immune memory, providing a compelling rationale for clinical translation in treating high-risk HCC patients.
Contact author name: Xuezhen Zeng, Department of Liver Surgery; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. E-mail address:zengxzh7@mail.sysu.edu.cn.
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Funder: This study is funded by the National Natural Science Foundation of China to Xuezhen Zeng (No. 82372777) and the Kelin Foundation for Distinguished Young Scholars to Xuezhen Zeng (No. R07014).
Conflict of interest: The authors declare that they have no conflict of interest.
See the article: Lei, K, et al., Anti-PD-1 synergizes with RFA to suppress abscopal tumors and induce durable memory against recurrence in HCC, Liver Res, Volume 9, Issue 2, 2025, Pages 132-143, https://doi.org/10.1016/j.livres.2025.05.003.
