title: Failure recovery of circulating NKG2D+CD56dimNK cells in HBV-associated hepatocellular carcinoma after hepatectomy predicts early recurrence.
abstract: Dysfunction of natural killer (NK) cells has been implicated in the failure of antitumor immune responses in hepatocellular carcinoma (HCC) patients. However, the changes of NK profile in peripheral blood after surgery and tumor tissues of HCC patients, as well as the underlying reason and the significance are vague. Here, we observed that the frequencies of circulating NKG2D+CD56dimNK cells decreased significantly in HBV-related HCC and were negatively correlated with the levels of serum TGF-β and soluble MICA (sMICA).In vitroexperiments confirmed that the TGF-β and sMICA in tumor tissue homogenates, as well as sMICA in HCC cells culture supernatants could reduce the frequency of NKG2D+CD56dimNK cells. In addition, in HCC patients the lower frequency of circulating NKG2D+CD56dimNK cells was associated with larger tumor size and/or higher serum GGT. Noticeably, the frequency of NKG2D+CD56dimNK cells at one month after surgery usually failed to restore in early recurrent patients, and that frequency was negatively associated with early recurrence and shorter overall survival. These results suggest that declined frequency of NKG2D+CD56dimNK cells in HCC was associated with higher TGF-β and sMICA production, and low frequency of circulating NKG2D+CD56dimNK cells at one month after surgery may predict poor prognosis of HBV-related HCC patients accepting hepatectomy.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs; The Department of Microbiology & Infectious Disease Center; School of Basic Medicine; Peking University Health Science Center; Beijing, China; These authors made equal contributions to this manuscript.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs; The Department of Microbiology & Infectious Disease Center; School of Basic Medicine; Peking University Health Science Center; Beijing, China; These authors made equal contributions to this manuscript.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Duan
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery; Affiliated Tumor Hospital of Zhengzhou University ; Zhengzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs; The Department of Microbiology & Infectious Disease Center; School of Basic Medicine; Peking University Health Science Center ; Beijing, China.
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs; The Department of Microbiology & Infectious Disease Center; School of Basic Medicine; Peking University Health Science Center ; Beijing, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Long
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs; The Department of Microbiology & Infectious Disease Center; School of Basic Medicine; Peking University Health Science Center ; Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tu
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control; National Center for AIDS/STD Control and Prevention; Chinese Center for Disease Control and Prevention; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases ; Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Immunology; Peking University Health Science Center ; Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs; The Department of Microbiology & Infectious Disease Center; School of Basic Medicine; Peking University Health Science Center ; Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs; The Department of Microbiology & Infectious Disease Center; School of Basic Medicine; Peking University Health Science Center ; Beijing, China.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Lu
keywords: HCC; NK cells; NKG2D; TGF-β; sMICA