A immunotherapy for primary non small cell lung cancer with Vα24 NKT cells

即使进行强化治疗，原发性肺癌也很难治愈。大约一半或更多的肺癌患者，即使是那些接受了完全切除的患者，临床上也没有发现局部或远处的微转移。由于肺癌术后随诊时常可见肺内复发，控制肺内转移对改善预后尤为重要。我们报道了在小鼠肺转移模型中，α-GalCer冲击的DC激活VαL4NKT细胞并清除已建立的转移灶，静脉注射α-GalCer冲击的DC到达肺并导致内源性Vα14NKT细胞的激活。人肺组织中Vα24NKT细胞数量与小鼠肺中Vα14NKT细胞数量相当，肿瘤组织中也有相当数量的Vα24NKT细胞浸润。这一观察还表明，外周血V-α24NKT细胞数量的减少对于使用α-GalCer负载的DC进行临床免疫治疗并不是一个明显的问题。在这里，我们监测了接受α-GalCer冲击的DC的小鼠肺中Vα14NKT细胞的数量，发现显著增加的Vα24NKT细胞持续存在。因此，当给予α-GalCer脉冲的DC时，我们可以预期在人类中具有类似的强大的抗肿瘤作用。我们的结果表明，α-GalCer冲击的DC可以根除癌症根治手术后患者肺部的微转移。我们确定了临床应用的确切条件，α-GalCer脉冲DC疗法有可能成为肺癌患者的一种新的免疫疗法。

Primary lung cancer is hard to cure, even with intensive treatments. Approximately half or more of lung carcinoma patients, even those undergoing complete resection, had clinically undetectable local or distant micrometastases. Since intrapulmonary recurrence is commonly observed during postoperative follow-up of lung cancer, control of intrapulmonary metastases is particularly important for improving prognosis. We reported that α-GalCer-pulsed DCs activated Vαl4 NKT cells and eradicated established metastatic tumor foci in mouse lung metastasis models, and i.v.-injected α-GalCer-pulsed DCs reached to the lung and led to activation of endogenous Vα14 NKT cells. Equivalent amounts of Vα24 NKT cells appeared to exist in the human lung compared to Vα14 NKT cells in the mouse lung, and considerable numbers of Vα24 NKT cells infiltrated in the tumor tissue. This observation also suggests that the reduction of peripheral blood Vα24 NKT cell number is not a significant problem for clinical immunotherapy using α-GalCer-pulsed DCs. Here, we monitored the number of Vα14 NKT cells in the lung of mice receiving α-GalCer-pulsed DCs and found that significantly increased Vα24 NKT cells were sustained . Thus, we may expect similarly potent antitumor effects in humans when α-GalCer-pulsed DCs are administered. Our results suggest that micrometastasis in the lung of patients following radical surgery of cancer can be eradicated when α-GalCer-pulsed DCs are administered. We determined the precise conditions for clinical, application, α-GalCer-pulsed DC therapy might become a new' immunotherapy for lung cancer patients.