Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan.
J Gastroenterol Hepatol. 2021 Jul;36(7):1988-1996. doi: 10.1111/jgh.15398. Epub 2021 Jan 28.
Hepatocellular carcinoma (HCC) remains a serious cause of cancer-related deaths worldwide. Developing new therapeutic strategies is urgently needed to improve the outcomes of HCC patients. Dendritic cell (DC)-based vaccines and programmed death 1 (PD-1) immune checkpoint inhibitors have been regarded as potential immunotherapeutics for HCC. However, the therapeutic efficacy of combining these two treatments for HCC remains to be evaluated.
In this study, DCs were derived from mouse bone marrow and pulsed with mouse HCC cell lysates to generate a DC vaccine. A monoclonal antibody that blocks the interaction of mouse PD-1 with its ligands was used as a PD-1 inhibitor. An orthotopic HCC mouse model was established to assess the effect of a DC vaccine in combination with a PD-1 inhibitor on overall survival and tumor volume.
Compared with the untreated control, single treatment with a DC vaccine or PD-1 inhibitor prolonged the overall survival and reduced the tumor volume of HCC mice. Further, compared with the single treatment with the DC vaccine or the PD-1 inhibitor, a combination treatment using both agents elicited a higher cytotoxicity of T cells against HCC cells and resulted in a better overall survival, smaller tumor volume, and greater tumor cell apoptosis in HCC mice.
Our results suggest that a combination treatment with DC vaccine and PD-1 inhibitor may be a promising therapeutic strategy for HCC.
肝细胞癌（HCC）仍然是全球癌症相关死亡的一个严重原因。开发新的治疗策略迫切需要改善 HCC 患者的预后。树突状细胞（DC）疫苗和程序性死亡 1（PD-1）免疫检查点抑制剂已被认为是 HCC 的潜在免疫疗法。然而，联合这两种治疗方法治疗 HCC 的疗效仍有待评估。
在这项研究中，从小鼠骨髓中提取 DC，并对其进行小鼠 HCC 细胞裂解物的脉冲处理，以生成 DC 疫苗。一种阻断小鼠 PD-1 与其配体相互作用的单克隆抗体被用作 PD-1 抑制剂。建立了一个原位 HCC 小鼠模型，以评估 DC 疫苗联合 PD-1 抑制剂对总生存期和肿瘤体积的影响。
与未治疗的对照组相比，单独使用 DC 疫苗或 PD-1 抑制剂可延长 HCC 小鼠的总生存期并减少肿瘤体积。此外，与单独使用 DC 疫苗或 PD-1 抑制剂相比，联合使用两种药物的治疗方案可引起针对 HCC 细胞的更高的 T 细胞细胞毒性，并在 HCC 小鼠中产生更好的总生存期、更小的肿瘤体积和更大的肿瘤细胞凋亡。
我们的研究结果表明，DC 疫苗和 PD-1 抑制剂的联合治疗可能是 HCC 的一种有前途的治疗策略。
