Efficient generation of highly immunocompetent dendritic cells from peripheral blood of patients with hepatitis C virus-related hepatocellular carcinoma.
Efficient generation of highly immunocompetent dendritic cells from peripheral blood of patients with hepatitis C virus-related hepatocellular carcinoma.
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DOI：
10.1016/j.intimp.2014.05.023
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发表时间：
2014-08
影响因子：
5.6
通讯作者：
M. Kitahara;E. Mizukoshi;Y. Nakamoto;N. Mukaida;K. Matsushima;S. Kaneko
中科院分区：
文献类型：
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作者：
M. Kitahara;E. Mizukoshi;Y. Nakamoto;N. Mukaida;K. Matsushima;S. Kaneko
背景与目的树突状细胞（dendritic cells，DC）免疫治疗是一种很有前途的肿瘤治疗方法。这种治疗的成功取决于诱导的DC的功能。然而，在体外制备DC用于肝细胞癌（HCC）患者免疫治疗的最佳条件上尚未达成共识。为了解决相关问题，我们评估了程序，以诱导DC，有效地在丙型肝炎病毒（HCV）相关hcch.MethodsWe研究了14例肝癌患者的免疫学数据。流式细胞术分析DC的制备和表面标志物。四种不同的额外激活刺激（方法I：单独培养基;方法II：用OK-432;方法III：用IL-1β + IL-6 + TNF-α;方法IV.用IL-1β + IL-6 + TNF-α + PGE 2）检测DC的吞噬功能，结果正常对照组和肝癌患者外周血中DC的数量和细胞因子的产生能力无明显差异。HCC患者MLR中DC的T细胞刺激活性显著低于健康对照组。结论OK-432是一种高免疫活性DC的候选药物，有望成为HCV相关HCC患者免疫治疗的关键药物。
Background & aimsImmunotherapy using dendritic cells (DCs) is a promising cancer therapy. The success of this therapy depends on the function of induced DCs. However, there has been no consensus on optimal conditions for DC preparation in vitro for immunotherapy of hepatocellular carcinoma (HCC) patients. To address relevant issues, we evaluated the procedures to induce DCs that efficiently function in hepatitis C virus (HCV)-related HCC.MethodsWe studied immunological data from 14 HCC patients. The DC preparation and the surface markers were assessed by flow cytometric analysis. Four different additional activation stimuli (Method I, medium alone; Method II, with OK-432; Method III, with IL-1β + IL-6 + TNF-α; Method IV, with IL-1β + IL-6 + TNF-α + PGE2) were tested and the functions of DCs were confirmed by examination of the ability of phagocytosis, cytokine production and allogeneic mixed lymphocyte reaction (MLR).ResultsThe numbers of DCs induced and their cytokine production ability were not different between healthy controls and HCC patients. T-cell stimulatory activity of DCs in MLR was significantly lower in HCC patients than in healthy controls. The maturation of DCs with OK-432 boosted production of cytokines and chemokines, such as IL-2, IL-12p70, IFN-γ, TNF-α, IL-13 and MIP1α, and restored T-cell stimulatory activity of DCs in MLR.ConclusionsThe clinically approved compound OK-432 is a candidate for highly immunocompetent DC preparation and may be considered as a key drug for immunotherapy of HCV-related HCC patients.