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In addition to CD8<jats:sup>+<\/jats:sup> T lymphocytes, natural killer (NK) cells represent promising therapeutic targets for hepatocellular carcinoma, because they comprise 30%\u201350% of all lymphocytes in the liver and contribute to antitumor immunity. A recent meta\u2010analysis revealed that the percentage of infiltrating NK cells in hepatocellular carcinoma correlates with a better patient outcome. Similarly, our previous genome\u2010wide association study on chronic viral hepatitis showed that a single\u2010nucleotide polymorphism of major histocompatibility complex class\u00a0I polypeptide\u2010related sequence\u00a0A (MICA), a ligand to the NK activating receptor, plays a critical role in hepatocarcinogenesis. In this review, we summarize the mechanisms underlying the regulation of MICA and NK group 2D expression in chronic hepatitis. Furthermore, we describe recent reports on MICA single\u2010nucleotide polymorphism\u2010driven hepatocarcinogenesis. The suppression of MICA shedding could represent a promising approach for immunosurveillance, as increased expression of membrane\u2010bound MICA achieved through the use of a MICA shedding inhibitor also enhances NK cell\u2010mediated cytotoxicity.<\/jats:p>","DOI":"10.1111\/hepr.14038","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T16:14:33Z","timestamp":1711556073000},"page":"420-428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Natural killer group\u00a02D\u2010major histocompatibility complex class\u00a0I polypeptide\u2010related sequence\u00a0A activation enhances natural killer cell\u2010mediated immunity against hepatocellular carcinoma: A review"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5902-6246","authenticated-orcid":false,"given":"Jun","family":"Arai","sequence":"first","affiliation":[{"name":"Department of 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