α-半乳糖神经酰胺致敏抗原提呈细胞后，肿瘤微环境中活化的不变自然杀伤 T 细胞的积累。
Accumulation of activated invariant natural killer T cells in the tumor microenvironment after α-galactosylceramide-pulsed antigen presenting cells.
机构信息
Department of Immunology, Graduate School of Medicine, Chiba University, Clinical Research Center, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
出版信息
J Clin Immunol. 2012 Oct;32(5):1071-81. doi: 10.1007/s10875-012-9697-9. Epub 2012 Apr 26.
PURPOSE
The intravenous administration of α-Galactosylceramide (α-GalCer)-pulsed antigen presenting cells (APCs) is well tolerated and the increased IFN-γ 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 α-GalCer-pulsed APCs to clarify the mechanisms of these findings, while especially focusing on the precise tumor site.
METHODS
Patients with operable advanced lung cancer received an intravenous injection of α-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.
RESULTS
Four patients completed the study protocol. We observed a significant increase in iNKT cell numbers in the TILs and augmented IFN-γ production by the α-GalCer-stimulated TILs.
CONCLUSION
The administration of α-GalCer-pulsed APCs successfully induced the dramatic infiltration and activation of iNKT cells in the tumor microenvironment.
目的
静脉注射α-半乳糖神经酰胺（α-GalCer）-脉冲抗原呈递细胞（APCs）具有良好的耐受性，并且治疗后外周血中产生 IFN-γ 的细胞增加似乎与延长生存时间有关。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。
方法
接受手术治疗的可切除晚期肺癌患者在术前接受 α-GalCer 脉冲 APC 静脉注射。收集切除的肺组织和肿瘤浸润淋巴细胞（TILs）以及外周血单核细胞，并分析不变自然杀伤 T（iNKT）细胞特异性免疫反应。
结果
4 例患者完成了研究方案。我们观察到 TILs 中 iNKT 细胞数量显著增加，并且 α-GalCer 刺激的 TILs 产生 IFN-γ 的能力增强。
结论
α-GalCer 脉冲 APC 的给药成功诱导了肿瘤微环境中 iNKT 细胞的剧烈浸润和激活。
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