Anti-PD-1 synergizes with RFA to suppress abscopal tumors and induce durable memory against recurrence in HCC.

Background and aims: Radiofrequency ablation (RFA) is the first-line treatment for early-stage hepatocellular carcinoma (HCC). However, recurrence after curative RFA remains a significant challenge for HCC patients. Although RFA induces an immune response, the anti-tumor effect is often limited by the immunosuppressive tumor microenvironment. Enhancing anti-tumor immunity is essential to improve treatment efficacy and prevent recurrence. In this study, we explore the efficacy and underlying mechanisms of the combination of RFA and anti-PD-1 in suppressing abscopal and recurrent tumors. Methods: We established a bilateral subcutaneous HCC mouse model and performed complete RFA on the right-flank tumor. Anti-PD-1 or anti-IgG was administered post-RFA. Tumor growth, immune cell profiles, and molecular pathways were assessed using flow cytometry, immunohistochemistry staining, RNA-sequencing, and Western blot. Chemokines released by the tumor were detected by ELISA. An Results: RFA combined with anti-PD-1 significantly suppressed abscopal tumor growth and prolonged survival. Compared with RFA monotherapy, the infiltration of CD8 Conclusions: Our study discovered that RFA combined with anti-PD-1 induced anti-tumor immunity to inhibit abscopal tumors and durable immune memory to prevent recurrence, suggesting RFA+anti-PD-1 as a potential therapeutic strategy for multifocal HCC and preventing recurrence.