Stimulation of autologous antitumor T-cell responses against medullary thyroid carcinoma using tumor lysate-pulsed dendritic cells.
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.
Bachleitner-Hofmann
T
T
Department of Surgery, University of Vienna Medical School, Vienna, Austria 1090.
Stift
A
A
Friedl
J
J
Pfragner
R
R
Radelbauer
K
K
Dubsky
P
P
Schüller
G
G
Benkö
T
T
Niederle
B
B
Brostjan
C
C
Jakesz
R
R
Gnant
M
M
D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D013964:Thyroid Neoplasms / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I