Stimulation of Autologous Antitumor T-Cell Responses Against Medullary Thyroid Carcinoma Using Tumor Lysate-Pulsed Dendritic Cells

Abstract

Dendritic cells (DCs) have attracted wide interest because of their unique capacity to elicit primary and secondary antitumor responses. We have generated autologous tumor lysate-pulsed DCs from three patients with medullary thyroid carcinoma (MTC) and tested them for their ability to stimulate cytotoxic T-cell responses against autologous MTC tumor cells in vitro. The aim of our investigations was to evaluate the potential efficacy of DC-based immunotherapy in patients with MTC. DCs were generated from peripheral blood monocytes using GM-CSF and IL-4 (immature DCs) or GM-CSF, IL-4, and TNFalpha (mature DCs). Our results indicate that mature tumor lysate-pulsed DCs are able to elicit a human leukocyte antigen class I-restricted cytotoxic T-cell response against autologous MTC tumor cells, whereas immature tumor lysate-pulsed DCs do not stimulate significant antitumor activity. We feel that our data may be relevant for future clinical trials of active immunotherapy using tumor lysate-pulsed DCs in patients with MTC who have residual or distant disease after surgical treatment. The fact that mature DCs displayed a substantially higher capacity to stimulate autologous antitumor T-cell responses than immature DCs underlines the importance of a maturation step in immunotherapy protocols based on DCs.

Dendritic Cell Vaccination in Medullary Thyroid Carcinoma

“…The clinical and radiomorphological improvements are particularly remarkable, given the far-advanced clinical stage of the disease and the current lack of conventional treatment options for these patients. Thus, based on the in vitro and in vivo investigations, we suggest that MTC is particularly well suited for DC-based immunotherapy (23,24). We believe that additional studies are justified to confirm and extend these highly promising results.…”

“…However, the extent to which the application of DC-based immunotherapy is effective in MTC has yet to be investigated more comprehensively. We have established recently an experimental tumor model for MTC using DCs, lymphocytes, and MTC cell lines in vitro under autologous conditions (24). We could demonstrate that mature, tumor lysate-pulsed DCs obtained from patients with MTC can prime a HLA class I-restricted antitumor T-cell response against autologous tumor cells.…”

Dendritic cells in autoimmune disorders and cancer of the thyroid

“…In Ret/Cal mice (regarded as an animal model of MTC) vaccination with amino acid-modified calcitonin-pulsed DCs resulted in diminished tumour outgrowth [101]. Few cases of partial disease stabilization were also observed in several small series of medullary thyroid carcinoma studies and in a single study with PTC and follicular carcinoma patients vaccinated with autologous DCs preincubated with tumour lysates [102][103][104][105][106]. However, taking in consideration rather mediocre clinical benefits, further research is needed to enhance the anti-tumour activity of DC-based anti -tumour vaccines in thyroid carcinomas.…”