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树突状细胞疫苗接种后甲状腺髓样癌中的降钙素特异性抗肿瘤免疫

Calcitonin-specific antitumor immunity in medullary thyroid carcinoma following dendritic cell vaccination.

作者信息

Schott Matthias, Feldkamp Joachim, Klucken Melanie, Kobbe Guido, Scherbaum Werner A, Seissler Jochen

机构信息

Department of Endocrinology, Heinrich Heine University Dusseldorf, Moorenstrasse 5, 40225 Dusseldorf, Germany.

出版信息

Cancer Immunol Immunother. 2002 Dec;51(11-12):663-8. doi: 10.1007/s00262-002-0325-z. Epub 2002 Oct 29.

Abstract

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.

摘要

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。

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