Restoration of natural killer activity in hepatocellular carcinoma by treatment with antibody against granulin-epithelin precursor
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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-gamma 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.
All Author(s) ListCheung PFY, Yip CW, Ng LWC, Wong CK, Cheung TT, Lo CM, Fan ST, Cheung ST
Journal nameOncoImmunology
Detailed descriptionDOI: 10.1080/2162402X.2015.1016706.
Year2015
Month1
Day1
Volume Number4
Issue Number7
PublisherTAYLOR & FRANCIS INC
ISSN2162-4011
LanguagesEnglish-United Kingdom
Keywordscytotoxicity; interferon-gamma; member D; MHC class I chain-related molecule A; natural-killer group 2; perforin
Web of Science Subject CategoriesImmunology; Oncology

Last updated on 2020-25-11 at 00:04