Natural killer cell dysfunction in hepatocellular carcinoma and NK cell-based immunotherapy.
Natural killer cell dysfunction in hepatocellular carcinoma and NK cell-based immunotherapy.
复制标题
肝细胞癌中自然杀伤细胞功能障碍和基于 NK 细胞的免疫治疗
DOI：
10.1038/aps.2015.41
复制
发表时间：
2015-10
影响因子：
8.2
通讯作者：
Tian ZG
中科院分区：
文献类型：
--
作者：
Sun C;Sun HY;Xiao WH;Zhang C;Tian ZG
B型肝炎病毒（HBV）和丙型肝炎病毒（HCV）感染与肝细胞癌（HCC）的关系机制尚不清楚。自然杀伤（NK）细胞占肝脏淋巴细胞总数的25%-50%，提示NK细胞在肝脏免疫中起重要作用。肝癌患者血液和肿瘤组织中NK细胞的数量与其生存和预后呈正相关。此外，肝癌组织中的一组NK细胞相关基因与生存期延长呈正相关。这些事实表明NK细胞和HCC进展密切相关。本文综述了慢性HBV和HCV感染患者NK细胞的异常及其功能障碍，这些异常和功能障碍有助于HCC的进展。然后，我们总结了NK细胞与肝癌的基础上的异常的血液和肝脏NK细胞的数量和表型的HCC患者。特别是，代表较低细胞毒性和受损的细胞因子产生的NK细胞的耗竭可以作为HCC发生的预测因子。最后，我们介绍了目前在小鼠肝癌模型和临床试验中进行的NK细胞免疫治疗的成就，强调了化学免疫治疗，NK细胞转移，基因治疗，细胞因子治疗和mAb治疗如何改善NK细胞在HCC治疗中的功能。基于NK细胞的抗HCC治疗策略单独使用或与其他疗法联合使用将是HCC治疗的巨大希望。
The mechanisms linking hepatitis B virus (HBV) and hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) remain largely unknown. Natural killer (NK) cells account for 25%–50% of the total number of liver lymphocytes, suggesting that NK cells play an important role in liver immunity. The number of NK cells in the blood and tumor tissues of HCC patients is positively correlated with their survival and prognosis. Furthermore, a group of NK cell-associated genes in HCC tissues is positively associated with the prolonged survival. These facts suggest that NK cells and HCC progression are strongly associated. In this review, we describe the abnormal NK cells and their functional impairment in patients with chronic HBV and HCV infection, which contribute to the progression of HCC. Then, we summarize the association of NK cells with HCC based on the abnormalities in the numbers and phenotypes of blood and liver NK cells in HCC patients. In particular, the exhaustion of NK cells that represents lower cytotoxicity and impaired cytokine production may serve as a predictor for the occurrence of HCC. Finally, we present the current achievements in NK cell immunotherapy conducted in mouse models of liver cancer and in clinical trials, highlighting how chemoimmunotherapy, NK cell transfer, gene therapy, cytokine therapy and mAb therapy improve NK cell function in HCC treatment. It is conceivable that NK cell-based anti-HCC therapeutic strategies alone or in combination with other therapies will be great promise for HCC treatment.