File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Restoration of natural killer activity in hepatocellular carcinoma by treatment with antibody against granulin-epithelin precursor

TitleRestoration of natural killer activity in hepatocellular carcinoma by treatment with antibody against granulin-epithelin precursor
Authors
Issue Date2015
PublisherTaylor & Francis Inc. The Journal's web site is located at http://www.tandfonline.com/koni
Citation
OncoImmunology, 2015, v. 4 n. 7, article no. e1016706, p. e1016706:1-12 How to Cite?
AbstractImpairment of natural killer (NK) cell activity is an important mechanism of tumor immunoevasion. We have previously shown that expression of granulin-epithelin precursor (GEP) in hepatocellular carcinoma (HCC) cells rendered the cells resistant to NK cell immunosurveillance. Here, we examined whether targeting GEP could rescue NK activity in HCC patients. The current study demonstrated that quantities and activities of NK cells were significantly lower in HCC patients compared with healthy individuals, and were negatively correlated with GEP levels in HCC cells. NK cells demonstrated enhanced expression of the stimulatory receptors natural-killer group 2, member D (NKG2D) and CD69, increased secretion of IFN-γ and perforin, and cytotoxicity against HCC cells upon GEP suppression. Opposite phenotypes of NK cells were observed when GEP was overexpressed in HCC cells. Importantly, GEP blockage by monoclonal antibody A23 restored NK activity in HCC patients and sensitized HCC cells to NK cytotoxicity. Furthermore, A23 induced NK-mediated antibody-dependent cell-mediated cytotoxicity against HCC. In summary, the activity of NK cells in HCC was impaired by GEP expression, which could be rescued by GEP antibody. This study provides new insight for treatments targeting GEP to boost NK activity in HCC patients. © 2015 Taylor & Francis Group, LLC.
Persistent Identifierhttp://hdl.handle.net/10722/217259
ISSN
2015 Impact Factor: 7.644
2015 SCImago Journal Rankings: 1.485
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheung, PFY-
dc.contributor.authorYip, CW-
dc.contributor.authorNg, LWC-
dc.contributor.authorWong, CK-
dc.contributor.authorCheung, TT-
dc.contributor.authorLo, CM-
dc.contributor.authorFan, ST-
dc.contributor.authorCheung, ST-
dc.date.accessioned2015-09-18T05:54:01Z-
dc.date.available2015-09-18T05:54:01Z-
dc.date.issued2015-
dc.identifier.citationOncoImmunology, 2015, v. 4 n. 7, article no. e1016706, p. e1016706:1-12-
dc.identifier.issn2162-402X-
dc.identifier.urihttp://hdl.handle.net/10722/217259-
dc.description.abstractImpairment of natural killer (NK) cell activity is an important mechanism of tumor immunoevasion. We have previously shown that expression of granulin-epithelin precursor (GEP) in hepatocellular carcinoma (HCC) cells rendered the cells resistant to NK cell immunosurveillance. Here, we examined whether targeting GEP could rescue NK activity in HCC patients. The current study demonstrated that quantities and activities of NK cells were significantly lower in HCC patients compared with healthy individuals, and were negatively correlated with GEP levels in HCC cells. NK cells demonstrated enhanced expression of the stimulatory receptors natural-killer group 2, member D (NKG2D) and CD69, increased secretion of IFN-γ and perforin, and cytotoxicity against HCC cells upon GEP suppression. Opposite phenotypes of NK cells were observed when GEP was overexpressed in HCC cells. Importantly, GEP blockage by monoclonal antibody A23 restored NK activity in HCC patients and sensitized HCC cells to NK cytotoxicity. Furthermore, A23 induced NK-mediated antibody-dependent cell-mediated cytotoxicity against HCC. In summary, the activity of NK cells in HCC was impaired by GEP expression, which could be rescued by GEP antibody. This study provides new insight for treatments targeting GEP to boost NK activity in HCC patients. © 2015 Taylor & Francis Group, LLC.-
dc.languageeng-
dc.publisherTaylor & Francis Inc. The Journal's web site is located at http://www.tandfonline.com/koni-
dc.relation.ispartofOncoImmunology-
dc.titleRestoration of natural killer activity in hepatocellular carcinoma by treatment with antibody against granulin-epithelin precursor-
dc.typeArticle-
dc.identifier.emailCheung, PFY: cphyllis@HKUCC-COM.hku.hk-
dc.identifier.emailYip, CW: wallacey@hku.hk-
dc.identifier.emailNg, LWC: lindanwc@hku.hk-
dc.identifier.emailCheung, TT: cheung68@hku.hk-
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hk-
dc.identifier.emailFan, ST: stfan@hku.hk-
dc.identifier.emailCheung, ST: stcheung@HKUCC.hku.hk-
dc.identifier.authorityLo, CM=rp00412-
dc.identifier.authorityFan, ST=rp00355-
dc.identifier.authorityCheung, ST=rp00457-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1080/2162402X.2015.1016706-
dc.identifier.pmid26140244-
dc.identifier.pmcidPMC4485783-
dc.identifier.scopuseid_2-s2.0-84944458608-
dc.identifier.hkuros254772-
dc.identifier.volume4-
dc.identifier.issue7-
dc.identifier.spagee1016706:1-
dc.identifier.epagee1016706:12-
dc.identifier.isiWOS:000356964800015-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats