Sequential therapy with immune checkpoint inhibitors and dendritic cells for advanced hepatocellular carcinoma

Advanced hepatocellular carcinoma (HCC) is an aggressive malignancy with poor prognosis. Immune checkpoint inhibitor (ICI) is an emerging immunotherapy for advanced HCC with a limited objective response. Dendritic cell (DC) can promote antigen-specific cytotoxicity of T cells. Sequential therapy with ICI and DC may promote antigen-specific immunity and improve therapeutic efficacy. Twenty-four patients with advanced HCC treated with sequential ICI and DC were included in this study. The treatment was undergone with nivolumab (3 mg/kg) or pembrolizumab (2 mg/kg) for 3–6 courses, and followed by 3 courses of autologous DCs which were propagated from peripheral blood monocytes and pulsed with tumor lysate. Among 24 patients, five patients were in BCLC stage B with large-sized or infiltrating type HCC, and 19 patients were in stage C. Seven patients had nivolumab and 17 patients had pembrolizumab treatment prior to DC therapy. The objective response and disease control rates were 16.7% and 70.8%, respectively, after short-term ICI therapy, and 41.7% and 75.0% after DC therapy. The patients with objective responses had lower pre-DC treatment neutrophil-to-lymphocyte ratio than the patients without objective response ( p = 0.028). For all 24 patients, the median overall survival was 36 months, and 1-, 2-, and 3-year overall survival rates were 87.5%, 75.0%, and 45.8%, respectively. Short course of ICI followed by DC therapy presents an acceptable therapeutic efficacy in this preliminary study. Sequential therapy with ICI and DC would be a potential combination for advanced HCC treatment, but a large-scale study is needed in the future.