The attenuated hepatocellular carcinoma-specific Listeria vaccine Lmdd-MPFG prevents tumor occurrence through immune regulation of dendritic cells.

Abstract

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.

• Authors: Xin Wan, Ci Cheng, Zhe Lin, Runqiu Jiang, Wei Zhao, Xin Yan, Junwei Tang, Kun Yao, Beicheng Sun, Yun Chen
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 11 Pg. 8822-38 (Apr 20 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25826093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Carrier Proteins
• Cytokines
• HLA-A2 Antigen
• Lmdd-MPFG vaccine
• NLR Family, Pyrin Domain-Containing 3 Protein
• Neoplasm Proteins
• Nlrp3 protein, mouse
• Nod1 Signaling Adaptor Protein
• Nod1 protein, mouse
• Nod2 Signaling Adaptor Protein
• Nod2 protein, mouse
• Receptors, Pattern Recognition
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Vaccines, Attenuated
• Vaccines, Synthetic

Topics

• Animals
• Cancer Vaccines (therapeutic use)
• Carrier Proteins (physiology)
• Cell Differentiation
• Cytokines (metabolism)
• Dendritic Cells (immunology, transplantation)
• Drug Screening Assays, Antitumor
• HLA-A2 Antigen (genetics, immunology)
• Humans
• Immunotherapy, Active
• Listeria monocytogenes (immunology)
• Liver Neoplasms, Experimental (immunology, therapy)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• NLR Family, Pyrin Domain-Containing 3 Protein
• Neoplasm Proteins (physiology)
• Nod1 Signaling Adaptor Protein (physiology)
• Nod2 Signaling Adaptor Protein (physiology)
• Receptors, Pattern Recognition (physiology)
• Spleen (immunology)
• T-Lymphocyte Subsets (immunology)
• Toll-Like Receptor 4 (physiology)
• Vaccines, Attenuated (therapeutic use)
• Vaccines, Synthetic (therapeutic use)