Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma: clinical safety
Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma: clinical safety
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DOI：
10.1111/j.1365-2249.2006.03290.x
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发表时间：
2007-02-01
影响因子：
4.6
通讯作者：
Kaneko, S.
中科院分区：
文献类型：
--
作者：
Nakamoto, Y.;Mizukoshi, E.;Kaneko, S.
肝细胞癌（HCC）的根治性治疗，包括手术切除和射频消融（RFA），并不能有效地预防肿瘤复发。基于树突状细胞（DC）的免疫疗法被认为有助于根除残留和复发的肿瘤细胞。目前的研究旨在评估经导管肝动脉栓塞（TAE）后DC输注肿瘤组织对肝硬化和HCC患者的安全性和生物活性。外周血单个核细胞（PBMCs）分化为表型证实的dc。10例患者在TAE治疗期间通过动脉导管给予自体dc。此后不久，一些HCC结节进行额外治疗以达到局部治疗效果。除了TAE引起的不良反应外，没有临床或血清学证据表明存在不良事件，包括任何患者的肝功能衰竭或自身免疫反应。在输注（111）铟标记的dc后，dc在HCC结节内和周围可检测到长达17天，并且与淋巴细胞和单核细胞浸润有关。有趣的是，在一些患者输注后4周，T淋巴细胞对肿瘤抗原Her-2/neu、MRP3、hTERT和AFP衍生的肽产生了反应。该策略对累积生存率无显著影响。这些结果表明，肝硬化和HCC患者在TAE治疗后经导管动脉DC输注肿瘤组织是可行且安全的。此外，抗原非特异性、不成熟的DC输注可能诱导对未引物的肿瘤抗原的免疫反应，为增强肿瘤免疫提供了一种合理的策略。
The curative treatments for hepatocellular carcinoma (HCC), including surgical resection and radiofrequency ablation (RFA), do not prevent tumour recurrence effectively. Dendritic cell (DC)-based immunotherapies are believed to contribute to the eradication of the residual and recurrent tumour cells. The current study was designed to assess the safety and bioactivity of DC infusion into tumour tissues following transcatheter hepatic arterial embolization (TAE) for patients with cirrhosis and HCC. Peripheral blood mononuclear cells (PBMCs) were differentiated into phenotypically confirmed DCs. Ten patients were administered autologous DCs through an arterial catheter during TAE treatment. Shortly thereafter, some HCC nodules were treated additionally to achieve the curative local therapeutic effects. There was no clinical or serological evidence of adverse events, including hepatic failure or autoimmune responses in any patients, in addition to those due to TAE. Following the infusion of (111)Indium-labelled DCs, DCs were detectable inside and around the HCC nodules for up to 17 days, and were associated with lymphocyte and monocyte infiltration. Interestingly, T lymphocyte responses were induced against peptides derived from the tumour antigens, Her-2/neu, MRP3, hTERT and AFP, 4 weeks after the infusion in some patients. The cumulative survival rates were not significantly changed by this strategy. These results demonstrate that transcatheter arterial DC infusion into tumour tissues following TAE treatment is feasible and safe for patients with cirrhosis and HCC. Furthermore, the antigen-non-specific, immature DC infusion may induce immune responses to unprimed tumour antigens, providing a plausible strategy to enhance tumour immunity.