Combined interleukin-12 and Dendritic cell neoadjuvant immunotherapy for hepatocellular carcinoma in immunosuppressed mice

当肝移植作为肝细胞癌（HCC）的治疗方法时，复发性HCC是最致命的并发症之一。原因之一是免疫抑制剂降低免疫力。本研究的目的是评估联合白细胞介素-12（IL-12）和树突状细胞（DC）新辅助免疫治疗在免疫抑制状态下对肝癌的疗效。C_3H小鼠（H-2k）。C.植入MH 134细胞（H-2k），并且我们用组合的瘤内电穿孔介导的鼠IL-12（mIL-12）和骨髓来源的基于DC的免疫疗法治疗建立的HCC。治疗后7天，我们开始使用FK 506 i。注射进入免疫控制状态。我们的研究结果表明，与mIL-12和DC联合治疗产生了大量的肿瘤内mIL-12和IFN-γ，并显示出更强的MH 134特异性细胞溶解活性比单独的mIL-12治疗和单独的DC治疗。mIL-12和DC联合治疗可显著抑制S. C.与单独的mIL-12治疗和单独的DC治疗相比，直接注射mIL-12载体和DC的HCC建立，以及减少自发性肺和肝转移。特别地，用mIL-12和DC的组合疗法未显示任何自发性肺和肝转移。提示IL-12联合DC新辅助免疫治疗是预防免疫抑制患者肝移植后肝癌复发的有效策略。

When liver transplantation is performed as a therapy for hepatocellular carcinoma (HCC), recurrent HCC is one of the most fatal complications. One of the reasons is the decrease of immunity by immunosuppressed agents. The aim of this study is to evaluate the efficacy of combined interleukin-12 (IL-12) and dendritic cell (DC) neoadjuvant immunotherapy for HCC under immunosuppression. C3H mice (H-2k) were s. c. implanted with MH134 cells (H-2k) and we treated the established HCC with combined intratumoral electroporation-mediated murine IL-12 (mIL-12) and bone marrow derived DC-based immunotherapy. 7 days after this therapy, we started the FK506 i. p. injection to put into the state of the immunity control. Our results demonstrated combined therapy with mIL-12 and DC produced highly amounts of intratumoral mIL-12 and IFN-γ and showed stronger MH134-specific cytolytic activity more than mIL-12 therapy alone and DC therapy alone. Combined therapy with mIL-12 and DC induced a significant suppression of the growth of s. c. established HCC into which the mIL-12 vector and DC had been directory injected compared to mIL-12 therapy alone and DC therapy alone, as well as reduced both spontaneous lung and liver metastases. In particularly, combined therapy with mIL-12 and DC did not show any spontaneous lung and liver metastases. These results suggest combined IL-12 and DC neoadjuvant immunotherapy is a potent effective strategy to prevent recurrences of HCC in immunosupressed patients undergone liver transplantation.