{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:10:04Z","timestamp":1790813404096,"version":"4.1.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T00:00:00Z","timestamp":1550102400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T00:00:00Z","timestamp":1550102400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p>The activating natural cytotoxicity receptor NKp30 is critical for natural killer (NK) cell function and tumor immune surveillance. The natural cytotoxicity receptor\u20103 (NCR3) gene is transcribed into several splice variants whose physiological relevance is still incompletely understood. In this study, we investigated the role of NKp30 and its major ligand B7 homolog 6 (B7\u2010H6) in patients with hepatocellular carcinoma (HCC). Peripheral blood NK cell phenotype was skewed toward a defective\/exhausted immune profile with decreased frequencies of cells expressing NKp30 and natural killer group 2, member D and an increased proportion of cells expressing T\u2010cell immunoglobulin and mucin\u2010domain containing\u20103. Moreover, NKp30\u2010positive NK cells had a reduced expression of NCR3 immunostimulatory splice variants and an increased expression of the inhibitory variant in patients with advanced tumor, resulting in deficient NKp30\u2010mediated functionality. Tumor\u2010infiltrating lymphocytes showed a prevalent inhibitory NKp30 isoform profile, consistent with decreased NKp30\u2010mediated function. Of note, there were significant differences in the cytokine milieu between the neoplastic and the surrounding non\u2010neoplastic tissue, which may have further influenced NKp30 function. Exposure of NK cells to B7\u2010H6\u2010expressing HCC cells significantly down\u2010modulated NKp30, that was prevented by small interfering RNA\u2013mediated knockdown, suggesting a role for this ligand in inhibiting NKp30\u2010mediated responses. Interestingly, B7\u2010H6 expression was reduced in HCC tissue and simultaneously augmented as a soluble form in HCC patients, particularly those with advanced staging or larger nodule size. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> These findings provide evidence in support of a role of NKp30 and its major ligand in HCC development and evolution.<\/jats:p>","DOI":"10.1002\/hep.30235","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T05:02:39Z","timestamp":1535605359000},"page":"1165-1179","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":65,"title":["Deficient Natural Killer Cell NKp30\u2010Mediated Function and Altered NCR3 Splice Variants in Hepatocellular Carcinoma"],"prefix":"10.1097","volume":"69","author":[{"given":"Stefania","family":"Mantovani","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medical Sciences and Infectious Diseases,Fondazione IRCCS Policlinico San Matteo,Pavia,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Oliviero","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medical Sciences and Infectious Diseases,Fondazione IRCCS Policlinico San Matteo,Pavia,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Therapeutics,University of Pavia,Italy"},{"name":"Division of Clinical Pathology,University Hospitals,Geneva,Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Varchetta","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medical Sciences and Infectious Diseases,Fondazione IRCCS Policlinico San Matteo,Pavia,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalila","family":"Mele","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medical Sciences and Infectious Diseases,Fondazione IRCCS Policlinico San Matteo,Pavia,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Sangiovanni","sequence":"additional","affiliation":[{"name":"CRC \u201cA. M. and A. Migliavacca\u201d Center for Liver Disease, Division of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Rossi","sequence":"additional","affiliation":[{"name":"Liver Transplant Unit, Fondazione IRCCS C\u00e0 Granda Ospedale Maggiore Policlinico,University of Milan,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Donadon","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and General Surgery,Humanitas Clinical and Research Center, Humanitas University,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Torzilli","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and General Surgery,Humanitas Clinical and Research Center, Humanitas 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