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

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.

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