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

Oncotarget. 2015 Apr 20;6(11):8822-38. doi: 10.18632/oncotarget.3558.

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.

Keywords: Lmdd-MPFG; PRRs; dendritic cells; hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / therapeutic use*
  • Carrier Proteins / physiology
  • Cell Differentiation
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Drug Screening Assays, Antitumor
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunotherapy, Active*
  • Listeria monocytogenes / immunology*
  • Liver Neoplasms, Experimental / immunology
  • Liver Neoplasms, Experimental / 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

Substances

  • 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