Nakamoto Yasunari, Kaneko Shuichi
Dept. of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
Gan To Kagaku Ryoho. 2010 Mar;37(3):413-6.
The current curative treatments for hepatocellular carcinoma (HCC) do not effectively prevent tumor recurrence. Dendritic cell (DC)-based immunotherapy can be a novel strategy targeting tumor recurrence. Here, we evaluated the bioactivity and beneficial effects of DC infusion of HCC tissues following transcatheter hepatic arterial embolization (TAE). 5x10(6) of monocyte- derived DCs were administered through an arterial catheter during TAE treatment procedures in patients with hepatitis C virus-related cirrhosis and HCC. In DC preparation, peptide-stimulated DCs [HLA-DR(+)CD86(+)CD14(-)] were phenotypically immature [CD80(low)CD83(low)], while OK-432-stimulated DCs highly expressed the activation marker CD83. Following the transfer, there was no clinical or serological evidence of adverse events in any patients in addition to those due to TAE. Most interestingly, survival analysis indicated that the patients treated with OK-432-stimulated DCs prolonged the recurrence-free survivals when compared with the historical controls treated with TAE alone. Collectively, OK- 432-stimulated DC transfer to HCC tissues following TAE treatment contributes to the induction of beneficial antitumor immune responses and the prolongation of recurrence-free survivals, providing a plausible strategy to reduce the tumor recurrence rates of HCC.
目前肝细胞癌(HCC)的治疗方法并不能有效预防肿瘤复发。基于树突状细胞(DC)的免疫疗法可能是一种针对肿瘤复发的新策略。在此,我们评估了经导管肝动脉栓塞术(TAE)后向HCC组织输注DC的生物活性和有益效果。在丙型肝炎病毒相关肝硬化和HCC患者的TAE治疗过程中,通过动脉导管给予5×10⁶个单核细胞衍生的DC。在DC制备过程中,肽刺激的DC [HLA-DR(+)CD86(+)CD14(-)]在表型上不成熟[CD80(低)CD83(低)],而OK-432刺激的DC高表达激活标志物CD83。转移后,除了TAE引起的不良事件外,没有任何患者出现临床或血清学证据表明有其他不良事件。最有趣的是,生存分析表明,与仅接受TAE治疗的历史对照组相比,接受OK-432刺激的DC治疗的患者无复发生存期延长。总体而言,TAE治疗后将OK-432刺激的DC转移至HCC组织有助于诱导有益的抗肿瘤免疫反应并延长无复发生存期,为降低HCC的肿瘤复发率提供了一种可行的策略。