Induction of peptide-specific immune response in patients with primary malignant melanoma of the esophagus after immunotherapy using dendritic cells pulsed with MAGE peptides.
Induction of peptide-specific immune response in patients with primary malignant melanoma of the esophagus after immunotherapy using dendritic cells pulsed with MAGE peptides.
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DOI：
10.1093/jjco/hyl136
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发表时间：
2007-02
影响因子：
2.4
通讯作者：
Y. Ueda;K. Shimizu;Tsuyoshi Itoh;N. Fuji;K. Naito;A. Shiozaki;Yoshiki Yamamoto;Takeshi Shimizu;Arihiro Iwamoto;H. Tamai;H. Yamagishi
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文献类型：
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作者：
Y. Ueda;K. Shimizu;Tsuyoshi Itoh;N. Fuji;K. Naito;A. Shiozaki;Yoshiki Yamamoto;Takeshi Shimizu;Arihiro Iwamoto;H. Tamai;H. Yamagishi
原发性食管恶性黑色素瘤（PMME）是一种非常罕见的疾病，预后极差。目前手术被认为是最好的治疗方法，而任何其他措施都无效。我们首次研究了使用单核细胞衍生的树突状细胞 (DC) 脉冲黑色素瘤相关抗原 (MAGE-1、MAGE-3) 表位肽对 PMME 患者术后的主动特异性免疫治疗的效果。患者同时接受了淋巴因子激活的杀伤细胞的被动免疫治疗。两名 HLA-A24 阳性 PMME 患者接受了治疗。两名患者最初均接受根治性食管切除术和区域淋巴结切除术，随后接受达卡巴嗪、尼莫司汀、长春新碱和干扰素-α 的辅助化疗。病例1患者术后21个月出现明显的腹部大淋巴结转移，采用主动特异性免疫治疗。疾病保持稳定 5 个月，患者在开始免疫治疗后存活了 12 个月。病例2患者在辅助化疗后尝试免疫治疗作为术后辅助治疗。免疫治疗后16个月内没有肿瘤复发。截至食管切除术后 49 个月，患者仍然活着。在这两名患者中，免疫治疗后，外周淋巴细胞响应肽刺激而在体外产生 IFN-γ 的能力显着增强，并且对 MAGE-3 肽的迟发型超敏反应皮试反应转为阳性。总之，使用 DC 和 MAGE 肽对 PMME 进行主动特异性免疫治疗是安全的，并且能够诱导肽特异性免疫反应。该病例报告值得对这种 PMME 免疫疗法进行进一步的临床评估。
Primary malignant melanoma of the esophagus (PMME) is a very rare disease with an extremely poor prognosis. Surgery is currently considered its best treatment, while any other measures are ineffective. We studied the effect of active specific immunotherapy using monocyte-derived dendritic cells (DCs) pulsed with the epitope peptides of melanoma-associated antigens (MAGE-1, MAGE-3) in patients with PMME after surgery, for the first time. The patient received passive immunotherapy with lymphokine-activated killer cells concomitantly. Two HLA-A24-positive patients with PMME were treated. Both patients initially received radical esophagectomy with regional lymphadenectomy, followed by adjuvant chemotherapy with dacarbazine, nimustine, vincristine and interferon-alpha. In the case 1 patient, active specific immunotherapy was used to treat a large abdominal lymph node metastasis that became obvious 21 months after surgery. The disease remained stable for 5 months, and the patient survived for 12 months after the initiation of immunotherapy. In the case 2 patient, immunotherapy was tried as post-operative adjuvant treatment after adjuvant chemotherapy. There was no tumor recurrence for 16 months after the immunotherapy. As of 49 months after esophagectomy, the patient is still alive. In both patients, the ability of peripheral lymphocytes to produce IFN-gamma in vitro in response to peptide stimulation was significantly enhanced and delayed-type hypersensitivity skin test response to MAGE-3 peptide was turned positive after immunotherapy. In conclusion, active specific immunotherapy for PMME with the use of DCs and MAGE peptides was safe and capable of inducing peptide-specific immune responses. This case report warrants further clinical evaluation of this immunotherapy for PMME.