Clinical application of NKT cell immune system for lung cancer

我们用α半乳糖神经酰胺脉冲树突状细胞治疗肺癌患者。晚期非小细胞肺癌或复发肺癌患者静脉注射α galcer脉冲dc (1x10^9/m^2)，以检验其安全性、可行性和临床反应。所有完成病例均进行免疫监测。符合条件的患者行外周血白细胞分离，收集外周血单个核细胞（PBMCs），密度梯度离心进一步分离。用人粒细胞-巨噬细胞集落刺激因子（GM-CSF）培养pbmc 1-2周，并在给药前一天用特异性配体α-半乳糖神经酰胺进行脉冲。17名患者参加了这项研究。采用流式细胞术（FACS）检测患者外周血NKT细胞频率，ELISPOT法检测外周血α - galcer再刺激后外周血IFN-γ的产生。α - galcer脉冲DC治疗后FN-γ产生明显增加的患者生存期和肿瘤进展时间相对较长，而IFN-γ产生反应不良的患者预后很差。这是首次报道IFN-γ在NKT细胞免疫治疗中的关键作用。基于这些结果，本文将对IFN-γ的产生和抗肿瘤免疫反应的作用和机制进行讨论。

We performed αGalactosylceramide-pulsed Dendritic cells in patients with lung cancer. Patients with advanced non-small cell lung cancer or recurrent lung cancer received intravenous injections of αGalCer-pulsed DCs (1x10^9/m^2) to test the safety, feasibility, and clinical response. Immunomonitoring was also performed in all completed cases. Eligible patients underwent peripheral blood leukapheresis, and peripheral blood mononuclear cells (PBMCs) were collected and further separated by density gradient centrifugation. PBMCs were cultured with human granulocyte-macrophage colony-stimulate factor (GM-CSF) for 1-2 weeks and pulsed with specific ligand, α-Galactosylceramide on the day before administration.Seventeen patients were enrolled in this study. The frequency of peripheral blood NKT cells in all patients was measured by FACS analysis and IFN-γ production after restimulation with αGalCer in PBMCs was measured by ELISPOT assay. Patients with marked increase of FN-γ production following the administration of αGalCer-pulsed DC showed relatively long survival and time to tumor progression, while poor responder of IFN-γ production showed very poor prognosis. This is the first report to show the crucial role of IFN-γ at NKT cell immunotherapy. With these results, the role and mechanisms of IFN-γ production and anti-tumor immune response will be discussed.