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The mechanisms underlying the regulation of NK cell activity are not completely understood. In this research, we identified the expression of taste receptor type 1 member 1 (T1R1) and taste receptor type 1 member 3 (T1R3) in a subset of hepatic NK cells in a mouse HCC model. T1R1 and T1R3 were selectively expressed in CD49a<jats:sup>+<\/jats:sup>CD49b<jats:sup>\u2212<\/jats:sup> NK cells in livers with HCC. In the in vitro cytotoxicity assay, amino acids promoted the tumoricidal effect of CD49a<jats:sup>+<\/jats:sup>CD49b<jats:sup>\u2212<\/jats:sup> NK cells through increasing the production of perforin, granzyme B and IFN\u2010\u03b3. Furthermore, using a lentivirus to induce the expression of exogenous T1R1 and T1R3 in normal hepatic NK cells, we found that amino acids enhanced NK cell\u2010mediated cytotoxicity on tumor cells through the T1R1\/T1R3 receptor, as demonstrated by more tumor cell lysis, up\u2010regulation of perforin and granzyme B in comparison with control NK cells. In addition, amino acids activated Akt and mechanistic target of rapamycin complex 1 (mTORC1) signaling in NK cells through T1R1\/T1R3 receptor. T\u2010bet expression in NK cells was also increased by amino acid treatment. Therefore, T1R1\/T1R3 receptor promotes the tumoricidal activity of hepatic CD49a<jats:sup>+<\/jats:sup>CD49b<jats:sup>\u2212<\/jats:sup> NK cells.<\/jats:p>","DOI":"10.1002\/eji.201847688","type":"journal-article","created":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T11:26:57Z","timestamp":1538047617000},"page":"2031-2041","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Taste receptor T1R1\/T1R3 promotes the tumoricidal activity of hepatic CD49a<sup>+<\/sup>CD49b<sup>\u2212<\/sup> natural killer cells"],"prefix":"10.1002","volume":"48","author":[{"given":"Shaoping","family":"Liu","sequence":"first","affiliation":[{"name":"Medical Research Center Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Wuhan Children's Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengliang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Zhongnan Hospital of Wuhan University Hubei Clinical Center and Key Laboratory for Intestinal and Colorectal Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Zhongnan Hospital of Wuhan University Hubei Clinical Center and Key Laboratory for Intestinal and Colorectal Diseases  Wuhan 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