Failure recovery of circulating NKG2D+CD56dimNK cells in HBV-associated hepatocellular carcinoma after hepatectomy predicts early recurrence

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⁺CD56^dimNK cells decreased significantly in HBV-related HCC and were negatively correlated with the levels of serum TGF-β and soluble MICA (sMICA). In vitro experiments 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⁺CD56^dimNK cells. In addition, in HCC patients the lower frequency of circulating NKG2D⁺CD56^dimNK cells was associated with larger tumor size and/or higher serum GGT. Noticeably, the frequency of NKG2D⁺CD56^dimNK 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⁺CD56^dimNK cells in HCC was associated with higher TGF-β and sMICA production, and low frequency of circulating NKG2D⁺CD56^dimNK cells at one month after surgery may predict poor prognosis of HBV-related HCC patients accepting hepatectomy.