Enhancement of tumor-specific T-cell responses by transcatheter arterial embolization with dendritic cell infusion for hepatocellular carcinoma

Enhancement of tumor-specific T-cell responses by transcatheter arterial embolization with dendritic cell infusion for hepatocellular carcinoma
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DOI:
10.1002/ijc.24882
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发表时间:
2010-05-01
影响因子:
6.4
通讯作者:
Kaneko, Shuichi
Kaneko, Shuichi
中科院分区:
医学1区
文献类型:
--
作者:
Mizukoshi, Eishiro;Nakamoto, Yasunari;Kaneko, Shuichi

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经导管动脉栓塞(TAE)通过诱导坏死和/或凋亡破坏肿瘤,并引起炎症和细胞因子产生,这可能有利于免疫激活和肿瘤特异性抗原的呈递。在目前的研究中,我们试图确定TAE对肿瘤特异性T细胞应答的影响以及TAE期间进行的树突状细胞(DC)输注的额外影响。肿瘤抗原特异性T细胞的患病率通过干扰素-γ酶联免疫斑点分析使用甲胎蛋白(AFP)和肿瘤抗原衍生肽分别在20和13例接受TAE和TAE与DC输注的肝细胞癌(HCC)患者中测定。TAE后20例患者中有6例观察到AFP特异性T细胞频率增加。在DC输注患者中观察到的频率高于单纯TAE患者。然而,尽管患者显示出增强的免疫应答,但肿瘤复发并没有完全预防。在时间过程分析中提供了增强的免疫应答是短暂的并且在3个月内减弱的证据。总之,与DC输注相比,TAE更有效地增强了肿瘤特异性免疫应答。虽然这种效果不足以预防HCC复发,但这些结果可能有助于开发新的HCC免疫治疗方法。
Transcatheter arterial embolization (TAE) destroys a tumor by the induction of necrosis and/or apoptosis and causes inflammation with cytokine production, which may favor immune activation and presentation of tumor-specific antigens. In the current study, we attempted to identify the effect of TAE on tumor-specific T-cell responses and the additional effect of dendritic cell (DC) infusion performed during TAE. The prevalence of tumor antigen-specific T cells was determined by interferon-gamma enzyme-linked immunospot analysis using alpha-fetoprotein (AFP) and tumor antigen-derived peptides in 20 and 13 patients with hepatocellular carcinoma (HCC) who received TAE and TAE with DC infusion, respectively. The increased frequency of AFP-specific T cells was observed in 6 of 20 patients after TAE. It was observed more frequently in patients with DC infusion than in those with TAE alone. However, tumor recurrence was not completely prevented in patients albeit displayed enhanced immune responses. The evidence that the enhanced immune responses were transient and attenuated within 3 months was provided in time-course analysis. In conclusion, TAE with DC infusion enhances the tumor-specific immune responses more effectively than TAE alone. Although the effect is not sufficient to prevent HCC recurrence, these results may contribute to the development of novel immunotherapeutic approach for HCC.