Dendritic cells pulsed with Hsp70 and HBxAg induce specific antitumor immune responses in hepatitis B virus-associated hepatocellular carcinoma

Mol Med Rep. 2016 Feb;13(2):1077-82. doi: 10.3892/mmr.2015.4654. Epub 2015 Dec 7.

Abstract

Previous studies have drawn attention to dendritic cell (DC) vaccines; particularly the application of the tumor-associated antigen-targeted DC vaccine. The present study analyzed DCs derived from a normal individual and pulsed the cells with heat shock protein 70 peptide (Hsp70) and/or hepatitis B virus x antigen (HBxAg), a hepatocellular carcinoma (HCC)-associated antigen. It was then investigated whether this method of vaccination induced strong therapeutic antitumor immunity. The results revealed that the Hsp70/HBxAg complex-activated phenotype improves the functional maturation of DCs compared with using Hsp70 or HBxAg alone. Compared with either Hsp70 or HBxAg alone, matured DCs pulsed with the Hsp70/HBxAg complex stimulated a high level of autologous T-cell proliferation and induced HCC-specific cytotoxic T lymphocytes, which specifically killed HCC cells through a major histocompatibility complex class I mechanism. These results indicated that a vaccination therapy using DCs co-pulsed with the Hsp70/HBxAg complex is an effective strategy for immunotherapy and may offer a useful approach to protect against HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / virology
  • Cell Death
  • Cell Differentiation
  • Cell Line, Tumor
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Flow Cytometry
  • HSP70 Heat-Shock Proteins / metabolism*
  • Hep G2 Cells
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Liver Neoplasms / immunology*
  • Mice, Nude
  • Mice, SCID
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • Trans-Activators / genetics
  • Trans-Activators / immunology*
  • Transfection
  • Viral Regulatory and Accessory Proteins
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, Viral
  • Biomarkers, Tumor
  • HSP70 Heat-Shock Proteins
  • RNA, Messenger
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein
  • L-Lactate Dehydrogenase