Wan Xin, Cheng Ci, Lin Zhe, Jiang Runqiu, Zhao Wei, Yan Xin, Tang Junwei, Yao Kun, Sun Beicheng, Chen Yun
Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Oncotarget. 2015 Apr 20;6(11):8822-38. doi: 10.18632/oncotarget.3558.
Immunotherapy is a promising treatment for liver cancer. Here, we tested the ability of the attenuated hepatocellular carcinoma-specific Listeria vaccine (Lmdd-MPFG) to treat hepatocellular carcinoma (HCC) in a mouse model. Immunization with the vaccine caused a strong anti-tumor response, especially in mice reinfused with dendritic cells (DCs). In mice that were also administered DCs, tumor suppression was accompanied by the strongest cytotoxic T lymphocyte response of all treatment groups and by induced differentiation of CD4+ T cells, especially Th17 cells. Additionally, the Lmdd-MPFG vaccine caused maturation of DCs in vitro. We demonstrated the synergistic effect of TLR4 and NLRP3 or NOD1 signaling pathways in LM-induced DC activation. These results suggest that the Lmdd-MPFG vaccine is a feasible strategy for preventing HCC.
免疫疗法是一种很有前景的肝癌治疗方法。在此,我们在小鼠模型中测试了减毒的肝细胞癌特异性李斯特菌疫苗(Lmdd-MPFG)治疗肝细胞癌(HCC)的能力。用该疫苗免疫引发了强烈的抗肿瘤反应,尤其是在重新注入树突状细胞(DC)的小鼠中。在同时给予DC的小鼠中,肿瘤抑制伴随着所有治疗组中最强的细胞毒性T淋巴细胞反应以及CD4+T细胞的诱导分化,尤其是Th17细胞。此外,Lmdd-MPFG疫苗在体外可使DC成熟。我们证明了TLR4和NLRP3或NOD1信号通路在李斯特菌诱导的DC激活中的协同作用。这些结果表明,Lmdd-MPFG疫苗是预防HCC的一种可行策略。