Antigen-loaded dendritic cells triggers a specific cytotoxic T lymphocytes immune response against hepatocellular carcinoma: in vitro study

Clin Transl Oncol. 2019 May;21(5):636-645. doi: 10.1007/s12094-018-1965-6. Epub 2018 Oct 27.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the common malignancies, characterized by poor response to conventional therapeutic options. Immunotherapy with dendritic cells (DCs)-vaccines is one of the most successful strategies used for the treatment of HCC. However, the methods applied in the preparation of antigen-loaded DCs are important factors for optimization of DCs vaccines.

Purpose: The present study was conducted to investigate the effect of HCC-whole tumor cell lysate prepared using rapid repetitive freeze-thaw cycles on the immunogenicity of DCs and evaluate the ability of whole tumor cell lysate-pulsed DCs vaccine to induce a specific cytotoxic T lymphocytes (CTLs) response against HepG2 cell line.

Methods: Immature DCs generated from peripheral blood monocytes were randomized into two groups: control DCs and whole tumor cell lysate-pulsed DCs. Phenotypic analysis of the DCs' cell maturation marker CD83 and co-stimulatory molecule CD86 was performed. HCC-specific cytotoxic activity of CD8+ CTLs was measured in vitro.

Results: Loading of DCs with necrotic whole cell lysate resulted in non-significant changes in DCs' expression of CD83, but a significant increase in expression of CD86. In addition, CD8+ CTLs stimulated with whole tumor cell lysate-pulsed DCs showed a high cytotoxic activity that specifically attack HepG2 cells.

Conclusion: Our findings indicated that pulsation of DCs with whole tumor cell lysate prepared by repetitive freeze-thaw cycles could efficiently enhance the ability of DCs to induce proliferation and clonal expansion of CD8+ CTLs. Data herein, also indicated that whole tumor cell lysate-pulsed DCs triggers a specific CD8+ CTLs against HCC tumor cells.

Keywords: CD8 cell; Cell immunotherapy; Dendritic cells; Hepatocellular carcinoma.

MeSH terms

  • Antigens, Neoplasm / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / pathology
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Hep G2 Cells
  • Humans
  • In Vitro Techniques
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / pathology
  • Monocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antigens, Neoplasm