RFA and anti-PD-1 combination therapy suppresses abscopal HCC tumors and prevents recurrence in mice

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.

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Contact the author: Xuezhen Zeng, Department of Liver Surgery; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. zengxzh7@mail.sysu.edu.cn.

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