Gemcitabine-treated pancreatic cancer cell medium induces the specific CTL antitumor activity by stimulating the maturation of dendritic cells

Int Immunopharmacol. 2014 Mar;19(1):10-6. doi: 10.1016/j.intimp.2013.12.022. Epub 2014 Jan 3.

Abstract

Gemcitabine (GEM) is a first line chemotherapeutic drug for advanced pancreatic cancer. Dendritic cell (DC) vaccine is a promising method of immunotherapy for malignant tumor. Recent research has indicated that gemcitabine can enhance the efficacy of DC vaccine, but precise mechanism is still unknown. Here, we aimed to investigate the effect of GEM on DCs. The results showed that GEM-treated pancreatic cancer cell medium stimulated maturation of DCs. When co-cultured with autologous T lymphocytes, the pulsed DCs promoted the proliferation of T cells, and exhibited specific cytotoxic T lymphocytes (CTLs) antitumor activity. Further research showed that stimulation of DC maturation may be related to the elevated level of Hsp70 induced by GEM. Our study indicates that GEM changes the immunogenicity of tumor cells, and enhances the efficacy of DC based immunotherapy for pancreatic cancer.

Keywords: Chemotherapy; Dendritic cell; Gemcitabine; Immunotherapy; Pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Culture Media
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Gemcitabine
  • HSP70 Heat-Shock Proteins / immunology*
  • Humans
  • Pancreatic Neoplasms / immunology*
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antimetabolites, Antineoplastic
  • Culture Media
  • HSP70 Heat-Shock Proteins
  • Deoxycytidine
  • Gemcitabine