Accumulation of Activated Invariant Natural Killer T Cells in the Tumor Microenvironment after α-Galactosylceramide-Pulsed Antigen Presenting Cells
Accumulation of Activated Invariant Natural Killer T Cells in the Tumor Microenvironment after α-Galactosylceramide-Pulsed Antigen Presenting Cells
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DOI：
10.1007/s10875-012-9697-9
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发表时间：
2012-10-01
影响因子：
9.1
通讯作者：
Nakayama, Toshinori
中科院分区：
文献类型：
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作者：
Nagato, Kaoru;Motohashi, Shinichiro;Nakayama, Toshinori
静脉注射α-氨基半乳糖神经酰胺(α-GalCer)冲击的抗原提呈细胞(APC)耐受性良好，治疗后外周血中产生干扰素-γ的细胞增加似乎与延长生存期有关。设计了一项探索性研究方案，术前给予α-GalCer脉冲APC以阐明这些发现的机制，同时特别关注精确的肿瘤部位。可手术的晚期肺癌患者在手术前接受静脉注射α-GalCer脉冲APC。收集切除的肺和肿瘤浸润性淋巴细胞(TIL)以及外周血单个核细胞，分析不变NKT(INKT)细胞特异性免疫反应。4名患者完成研究方案。我们观察到TIL中的iNKT细胞数量显著增加，并通过α-GalCer刺激的TIL增加干扰素-γ的产生。α-GalCer脉冲APC的给药成功地诱导了iNKT细胞在肿瘤微环境中的显著渗透和激活。
The intravenous administration of alpha-Galactosylceramide (alpha-GalCer)-pulsed antigen presenting cells (APCs) is well tolerated and the increased IFN-gamma producing cells in the peripheral blood after the treatment appeared to be associated with prolonged survival. An exploratory study protocol was designed with the preoperative administration of alpha-GalCer-pulsed APCs to clarify the mechanisms of these findings, while especially focusing on the precise tumor site.Patients with operable advanced lung cancer received an intravenous injection of alpha-GalCer-pulsed APCs before surgery. The resected lung and tumor infiltrating lymphocytes (TILs) as well as peripheral blood mononuclear cells were collected and the invariant NKT (iNKT) cell-specific immune responses were analyzed.Four patients completed the study protocol. We observed a significant increase in iNKT cell numbers in the TILs and augmented IFN-gamma production by the alpha-GalCer-stimulated TILs.The administration of alpha-GalCer-pulsed APCs successfully induced the dramatic infiltration and activation of iNKT cells in the tumor microenvironment.