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


CONCLUSIONS
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.
Gholamin
Mehran
M
Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran.
Moaven
Omeed
O
Farshchian
Moein
M
Mahmoudi
Mahmoud
M
Sankian
Mojtaba
M
Memar
Bahram
B
Forghani
Mohammad Naser
MN
Malekzadeh
Reza
R
Rajabi-Mashhadi
Mohammad Taghi
MT
Abbaszadegan
Mohammad Reza
MR
D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D002469:Cell Separation; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D018274:Electroporation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014182:Transplantation, Autologous
D019496:Cancer Vaccines; D012333:RNA, Messenger; D007371:Interferon-gamma