Combination therapy with dendritic cell vaccine and programmed death ligand 1 immune checkpoint inhibitor for hepatocellular carcinoma in an orthotopic mouse model

• Published in: Therapeutic advances in medical oncology Vol. 12; p. 1758835920922034
• Main Authors: Teng, Chiao-Fang, Wang, Ting, Wu, Tzu-Hua, Lin, Jia-Hui, Shih, Fu-Ying, Shyu, Woei-Cherng, Jeng, Long-Bin
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 2020; Sage Publications Ltd; SAGE Publishing
• Subjects: Apoptosis; Bone marrow; Cell death; Combination therapy; Cytotoxicity; Dendritic cells; Hepatocellular carcinoma; Hepatoma; Immune checkpoint; Ligands; Liver cancer; Lymphocytes T; Original Research; PD-L1 protein; Vaccines; combination therapy; programmed death ligand 1; immune checkpoint inhibitor; dendritic cells; hepatocellular carcinoma
• ISSN: 1758-8359; 1758-8340; 1758-8359
• DOI: 10.1177/1758835920922034

Background: Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite remarkable advances in treatment, high mortality in HCC patients remains a big challenge. To develop novel therapeutic strategies for HCC is thus urgently needed to improve patient survival. Dendritic cells (DC)-based vaccines can induce tumor-specific immunity and have emerged as a promising approach for treating HCC patients; however, its effectiveness needs to be improved. Recently, blockade of programmed death ligand 1 (PD-L1) immune checkpoint pathway has been shown to enhance anti-tumor immune responses and exhibited great potential in HCC therapy. Methods: In this study, we generated DC vaccine by pulsing the C57BL/6J mouse bone marrow-derived DC with mouse hepatoma Hep-55.1C cell lysate. We developed a therapeutic strategy combining DC vaccine and PD-L1 inhibitor for HCC and evaluated its efficacy in an orthotopic HCC mouse model in which Hep-55.1C cells were directly injected into left liver lobe of C57BL/6J mouse. Results: Compared with a control group of mice, groups of mice treated with DC vaccine or PD-L1 inhibitor had significantly improved overall survival, reduced tumor volume, and increased tumor cell apoptosis. Remarkably, combination treatment with DC vaccine and PD-L1 inhibitor led to considerably longer overall survival, smaller tumor volume, and higher tumor cell apoptosis of mice than either treatment alone in a dose-dependent manner through inducing a stronger anti-tumor cytotoxic T cell response. Conclusion: Our data suggested that combination therapy with DC vaccine and PD-L1 inhibitor might have great promise as a novel treatment strategy for HCC.