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

• Published in: The journal of clinical endocrinology and metabolism Vol. 87; no. 3; pp. 1098 - 1104
• Main Authors: Bachleitner-Hofmann, T, Stift, A, Friedl, J, Pfragner, R, Radelbauer, K, Dubsky, P, Schüller, G, Benkö, T, Niederle, B, Brostjan, C, Jakesz, R, Gnant, M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.03.2002; Copyright by The Endocrine Society
• Subjects: Adult; Aged; Biological and medical sciences; Carcinoma - immunology; Carcinoma - pathology; Cell Division - physiology; Cellular Senescence - physiology; Dendritic Cells - physiology; Endocrinopathies; Female; Histocompatibility Antigens Class I - analysis; Humans; Male; Malignant tumors; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Phenotype; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - pathology; T-Lymphocytes, Cytotoxic - physiology; Thyroid Neoplasms - immunology; Thyroid Neoplasms - pathology; Thyroid. Thyroid axis (diseases); Tumor Cells, Cultured; Antineoplastic agent; Ability; Human; Dendritic cell; Secondary; Monocyte; Cytotoxicity; Stimulation; Malignant tumor; In vitro; Blood; Surgery; Immunotherapy; T-Lymphocyte; Primary; Medullary carcinoma
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.87.3.8283

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 TNFα (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.