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Submitted on May 5, 2006
Accepted on August 29, 2006
Institutions: Department of Surgery (T.B.-H., M.S., P.K., M.S., P.D., H.H., S.S., M.G., J.F., A.S.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Pathophysiology (R.P.), Medical University of Graz, A-8010 Graz, Austria
* To whom correspondence should be addressed. E-mail: thomas.bachleitner-hofmann{at}meduniwien.ac.at.
Background. In vitro and in vivo studies have shown that dendritic cells (DCs) can stimulate antitumor T-cell responses against medullary thyroid carcinoma (MTC). However, despite promising results in selected cases, the clinical efficacy of DC immunotherapy in patients with MTC has been limited. Recently, it has been demonstrated in mice that heat shock enhances the capacity of bone marrow-derived DCs to stimulate antigen-specific T-cells. The aim of our investigations was to evaluate whether heat shock also increases the capacity of human monocyte-derived DCs to stimulate antitumor T-cell responses against MTC tumor cells. Methods. DCs from 6 patients with metastatic MTC were pulsed with tumor lysate derived from allogeneic MTC tumor cells and were heat shocked for 12 h at 40C or kept at 37C. Thereafter, the DCs were matured and cocultured with T-cells. Finally, the cytotoxic activity of T-cells against MTC tumor cells was measured in vitro. Results. In all patient samples cytotoxic T-cell responses against MTC tumor cells could be induced. Notably, heat shocked DCs were more potent stimulators of cytotoxic T-cell responses than control DCs, with T-cells stimulated with heat shocked DCs displaying a significantly increased cytotoxic activity against MTC tumor cells as compared with T-cells stimulated with control DCs. In none of the experiments a cytotoxic T-cell response against unrelated pancreatic tumor cells (PANC-1) was observed, using both control and heat shocked DCs. Conclusions. Our study shows that heat shocking DCs may be a valuable strategy to increase the immunostimulatory capacity of DCs used for immunotherapy of MTC.
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