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

• Published in: BMC cancer 2010-06, Vol.10 (1), p.261-261, Article 261
• Main Authors: Gholamin, Mehran, Moaven, Omeed, Farshchian, Moein, Mahmoudi, Mahmoud, Sankian, Mojtaba, Memar, Bahram, Forghani, Mohammad Naser, Malekzadeh, Reza, Rajabi-Mashhadi, Mohammad Taghi, Abbaszadegan, Mohammad Reza
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Cancer vaccines; Cancer Vaccines - pharmacology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - therapy; Care and treatment; Cell Separation; Cells, Cultured; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - transplantation; Electroporation; Esophageal cancer; Esophageal Neoplasms - genetics; Esophageal Neoplasms - immunology; Esophageal Neoplasms - therapy; Female; Flow Cytometry; Genetic aspects; Health aspects; Humans; Immunophenotyping; Interferon-gamma - immunology; Lymphocyte Activation; Male; Middle Aged; Physiological aspects; Prevention; RNA, Messenger - immunology; T-Lymphocytes, Cytotoxic - immunology; Transfection; Transplantation, Autologous
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-10-261

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). 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. 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). 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.