[Perioperative Immunotherapy as a Strategy to Overcome Hepatocellular Carcinoma]

Hepatocellular carcinoma (HCC) has a high recurrence rate even after curative resection or local ablation, and early recurrence within 1-2 years is often driven by intrahepatic metastasis and strongly affects prognosis. Immune checkpoint inhibitor (ICI)-based combination therapy has become a standard approach for unresectable advanced HCC, prompting efforts to extend immunotherapy to earlier-stage disease. Neoadjuvant immunotherapy may induce systemic antitumor immunity while tumor antigens remain abundant. However, definitive phase Ⅲ evidence for neoadjuvant therapy alone is lacking. In the adjuvant setting, large phase Ⅲ trials, including IMbrave050 and KEYNOTE-937, failed to show a sustained reduction in recurrence, highlighting the limitations of postoperative immunotherapy alone. In contrast, the phase Ⅲ CARES-009 trial, which connected neoadjuvant and adjuvant treatment into a perioperative strategy, reported suppression of postoperative recurrence, although longer follow-up is still required for a definitive evaluation. As a vaccine-based perioperative immunotherapy distinct from ICIs, we also demonstrated the safety of perioperative administration in resectable HCC and the potential to enhance intratumoral CD8-positive T-cell infiltration. In this review, we summarize the biological rationale and the principal clinical trial results of perioperative immunotherapy for resectable HCC, and outline its current positioning and future prospects.