MICA SNPs and the NKG2D system in virus-induced HCC

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• 作者：Kaku Goto ; Naoya Kato
• 关键词：MHC class I polypeptide ; related sequence A ; Single nucleotide polymorphism ; Hepatitis C virus ; Hepatitis B virus ; Hepatocellular carcinoma ; Natural killer
• 刊名：Journal of Gastroenterology
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：50
• 期：3
• 页码：261-272
• 全文大小：473 KB
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• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Gastroenterology
  Oncology
  Surgical Oncology
  Hepatology
  Internal Medicine
  Colorectal Surgery
  
• 出版者：Springer Japan
• ISSN：1435-5922

文摘

Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer-related death globally. Above well-known risk factors for HCC development ranging from various toxins to diseases such as diabetes mellitus, chronic infection with hepatitis B virus and hepatitis C virus (HCV) poses the most serious threat, constituting the cause in more than 80?% of cases. In addition to the viral genes intensively investigated, the pathophysiological importance of host genetic factors has also been greatly and increasingly appreciated. Genome-wide association studies (GWAS) comprehensively search the host genome at the single-nucleotide level, and have successfully identified the genomic region associated with a whole variety of diseases. With respect to HCC, there have been reports from several groups on single nucleotide polymorphisms (SNPs) associated with hepatocarcinogenesis, among which was our GWAS discovering MHC class I polypeptide-related sequence A (MICA) as a susceptibility gene for HCV-induced HCC. MICA is a natural killer (NK) group 2D (NKG2D) ligand, whose interaction with NKG2D triggers NK cell-mediated cytotoxicity toward the target cells, and is a key molecule in tumor immune surveillance as its expression is induced on stressed cells such as transformed tumor cells for the detection by NK cells. In this review, the latest understanding of the MICA-a href='/search?dc.title=NKG2D&facet-content-type=ReferenceWorkEntry&sortOrder=relevance' class='reference-link webtrekk-track' gaCategory="Internal link" gaLabel="NKG2D" gaAction="reference keyword">NKG2D system in viral HCC, particularly focused on its antitumor properties and the involvement of MICA SNPs, is summarized, followed by a discussion of targets for state-of-the-art cancer immunotherapy with personalized medicine in view.