title: 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.
authors.affiliation: Department of Surgery, University of Vienna Medical School, Vienna, Austria 1090.
authors.forename: T
authors.initials: T
authors.lastname: Bachleitner-Hofmann
authors.forename: A
authors.initials: A
authors.lastname: Stift
authors.forename: J
authors.initials: J
authors.lastname: Friedl
authors.forename: R
authors.initials: R
authors.lastname: Pfragner
authors.forename: K
authors.initials: K
authors.lastname: Radelbauer
authors.forename: P
authors.initials: P
authors.lastname: Dubsky
authors.forename: G
authors.initials: G
authors.lastname: Schüller
authors.forename: T
authors.initials: T
authors.lastname: Benkö
authors.forename: B
authors.initials: B
authors.lastname: Niederle
authors.forename: C
authors.initials: C
authors.lastname: Brostjan
authors.forename: R
authors.initials: R
authors.lastname: Jakesz
authors.forename: M
authors.initials: M
authors.lastname: Gnant
mesh_terms: 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
chemical_list: D015395:Histocompatibility Antigens Class I