Impairment of natural killer cell and dendritic cell functions by the soluble form of MHC class I-related chain A in advanced human hepatocellular carcinomas
Impairment of natural killer cell and dendritic cell functions by the soluble form of MHC class I-related chain A in advanced human hepatocellular carcinomas
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DOI：
10.1016/j.jhep.2005.05.026
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发表时间：
2005-12-01
影响因子：
25.7
通讯作者：
Hayashi, N
中科院分区：
文献类型：
--
作者：
Jinushi, M;Takehara, T;Hayashi, N
背景/目的：MHC i类相关链A （MICA）是人自然杀伤（NK）细胞刺激受体NKG2D的配体，在人肝细胞癌（HCC）中表达。早期的研究表明，MICA的可溶性形式（sMICA）从某些类型的肿瘤中释放出来，但其在HCC中的存在和作用尚未确定。方法：对26例HCC患者进行血清sMICA检测。体外实验检测sMICA对NK细胞NKG2D表达和随后的树突状细胞（DC）活化的影响。结果：sMICA水平在晚期HCC患者中经常升高。sMICA的升高与NKG2D表达下调和NK细胞活化受损有关。体外实验显示，晚期HCC来源的sMICA可下调NKG2D表达和NK细胞功能。NK细胞刺激人肝癌细胞诱导DC成熟，增强DC的异源刺激能力；用含smica的血清预处理NK细胞可完全消除DC的成熟和活化。结论：sMICA存在于晚期HCC患者的血清中，可能通过负性调节先天免疫和适应性免疫作为肿瘤逃避机制。(c) 2005年欧洲肝脏研究协会。Elsevier B.V.版权所有。
Background/Aims: MHC class I-related chain A (MICA), a human ligand of natural killer (NK) cell stimulatory receptor NKG2D, is expressed in human hepatocellular carcinomas (HCC). Earlier research demonstrated that the soluble form of MICA (sMICA) is released from some types of tumors, but its presence and role in HCC was not determined.Methods: Serum sMICA was studied in 26 patients with HCC. In vitro experiments were performed to examine the impact of sMICA on NK cell expression of NKG2D and subsequent dendritic cell (DC) activation.Results: The levels of sMICA were frequently elevated in patients with advanced HCC. The elevation of sMICA was associated with down-regulated NKG2D expression and impaired activation of NK cells. In vitro experiments revealed that sMICA derived from advanced HCC was responsible for down-modulation of NKG2D expression and NK cell functions. NK cells upon stimulation of human hepatoma cells induced maturation of DC and enhanced the allostimulatory capacity of DC; maturation and activation of DC were completely abolished when NK cells were pretreated with sMICA-containing serum.Conclusions: sMICA is present in sera of patients with advanced HCC and may serve as a tumor evasion mechanism by negatively modulating both innate and adaptive immunity. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.