Schott Matthias, Feldkamp Joachim, Klucken Melanie, Kobbe Guido, Scherbaum Werner A, Seissler Jochen
Department of Endocrinology, Heinrich Heine University Dusseldorf, Moorenstrasse 5, 40225 Dusseldorf, Germany.
Cancer Immunol Immunother. 2002 Dec;51(11-12):663-8. doi: 10.1007/s00262-002-0325-z. Epub 2002 Oct 29.
In this study, we investigated the immune response following immunotherapy with calcitonin-pulsed dendritic cells (DC) in 7 patients with metastasized medullary thyroid carcinoma. After immunization with 1-5 x 10(6) autologous DC, significant calcitonin-specific T cell proliferation was detectable in 3 patients. Measurement of cytokine release from T lymphocytes demonstrated high post-treatment interferon-gamma (IFN-gamma) secretion after stimulation with calcitonin in 5 patients, one of whom experienced significant tumor regression. In contrast, antigen-specific interleukin-4 (IL-4) production was only slightly increased in 4 patients. All 7 patients developed a strong delayed-type hypersensitivity (DTH) skin reaction, which was confirmed to be mediated by infiltrating CD4+ T-helper cells and CD8+ cytotoxic T cells in all 3 patients who underwent skin biopsy. This is the first study to show that a polypeptide hormone can be used to develop a DC vaccination strategy for the immunotherapy of highly malignant endocrine cancers.
在本研究中，我们调查了7例转移性甲状腺髓样癌患者接受降钙素脉冲树突状细胞（DC）免疫治疗后的免疫反应。在用1-5×10⁶个自体DC免疫后，3例患者可检测到显著的降钙素特异性T细胞增殖。对T淋巴细胞释放的细胞因子进行检测发现，5例患者在用降钙素刺激后治疗后干扰素-γ（IFN-γ）分泌量较高，其中1例患者出现明显的肿瘤消退。相比之下，4例患者抗原特异性白细胞介素-4（IL-4）的产生仅略有增加。所有7例患者均出现强烈的迟发型超敏反应（DTH）皮肤反应，在接受皮肤活检的所有3例患者中，均证实该反应由浸润的CD4⁺辅助性T细胞和CD8⁺细胞毒性T细胞介导。这是第一项表明多肽激素可用于制定DC疫苗接种策略以免疫治疗高度恶性内分泌癌的研究。
