Induction of cytotoxic T lymphocytes primed with tumor RNA-loaded dendritic cells in esophageal squamous cell carcinoma: preliminary step for DC vaccine design

BMC Cancer. 2010 Jun 7:10:261. doi: 10.1186/1471-2407-10-261.

Abstract

Background: Dendritic cells (DC) are potent antigen presenting cells with the ability to prime naïve T cells and convert them to cytotoxic T-lymphocytes (CTL). We evaluated the capability of autologous DCs transfected with total tumor and normal RNA to induce cytotoxic CTL as the preliminary step to design a DC-based vaccine in the esophageal squamous cell carcinoma (ESCC).

Methods: Monocytes-derived DCs were electroporated with either total tumor RNA or normal RNA. T cells were then primed with tumor RNA transfected DCs and lytic effects of the generated CTL were measured with Cytotoxicity assay and IFN-gamma Release Elispot assay.

Results: Cytotoxicity was induced against DCs loaded with tumoral RNA (%24.8 +/- 5.2 SEM) while in normal RNA-loaded DCs, it was minimal (%6.1 +/- 2.4 SEM) and significantly lower (p < 0.05). INF-gamma secretion was more than 2-folds higher in tumoral RNA-loaded DCs when compared with normal RNA-loaded DCs (p < 0.05).

Conclusion: Electroporating DCs with tumor RNA generated tumor antigen presenting cells which in turn enhanced cytotoxic effects of the T cells against ESCC. This may be a useful autologous ex vivo screening tool for confirming the lytic effects of primed T cells on tumors and evaluate probable further adverse effects on noncancerous tissues. These data provide crucial preliminary information to establish a total tumor RNA-pulsed DC vaccine therapy of ESCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cancer Vaccines / pharmacology*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / therapy*
  • Cell Separation
  • Cells, Cultured
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic*
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Electroporation
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / immunology
  • Esophageal Neoplasms / therapy*
  • Female
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Interferon-gamma / immunology
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • RNA, Messenger / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection
  • Transplantation, Autologous

Substances

  • Cancer Vaccines
  • RNA, Messenger
  • Interferon-gamma