Radiofrequency Ablation and Immunotherapy: Orchestrating the Immune Microenvironment for Improved Hepatocellular Carcinoma Control

Radiofrequency ablation (RFA) is a radical treatment modality for early-stage hepatocellular carcinoma (HCC). In addition to directly eliminating tumour cells, RFA induces changes in infiltrating cells within the liver tumour immune microenvironment (TIME), thereby eliciting anti-tumour immune effects. Moreover, incomplete radiofrequency ablation (IRFA) induces an immunosuppressive tumour microenvironment, which inhibits anti-tumour immune responses and promotes tumour recurrence and metastasis. Immunotherapy, a systemic treatment, activates or enhances the immune system to recognise and eliminate tumour cells. Thus, orchestrating the TIME makes it possible to combine RFA and immunotherapy, which may significantly enhance the anti-tumour immune response to target residual tumour cells. This combinatorial approach may emerge as a pivotal strategy to augment HCC control and mitigate post-RFA recurrence. This review discusses how RFA modulates the TIME in HCC, and the immune-related mechanisms leading to tumour cell survival and invasion after IRFA. Finally, we summarise the combined mechanisms of the two modalities on TIME, and their clinical implications for treating HCC, aiming to provide new insights for the combined strategy of RFA and immunotherapy.