Increased expression of activating receptors and up-regulated function of natural killer cells in peripheral blood of patients with HBV-related hepatocellular carcinoma

Abstract Background This study aimed to investigate and identify the characteristics of peripheral natural killer (NK) cells of hepatocellular carcinoma (HCC) patients who infected with hepatitis B virus. Methods Flow cytometry was utilized to identify the frequency and receptors of NK cells, in the meantime, to analyze the killing ability and cytotoxicity of NK cells of patients of which embraced 36 cases of HBV-associated HCC, 34 individuals who suffered in HBV-associated cirrhosis (LC) and 30 non-liver dysfunction healthy individuals as control (HC). Results Cell counts for NK and CD56dimNK were reduced in patients with HCC, however, there was no statistically significant. The count of CD56brightNK cells in the HCC subpopulation was remarkably higher than the subset of the HC (P < 0.05). The counts of activated receptors of NKG2D/p30 were elevated in patients with HCC, as well as the NKp44 and the NKp46. There was no statistically meaningful difference of inhibitory receptor expressions such as CD158a/b on peripheral NK cells of patients with HCC and LC and those with HC (P > 0.05). Following an IL-12 stimulation, the production of INF-γ/-α of patients with HCC was less than those produced by HC (P < 0.05). However, killing activity and cytotoxicity, as the primary responsibilities of the natural killer cells, were upregulated in HCC individuals. HBV associated individuals were found lower counts and capability to produce cytokines of natural killer cells. Nevertheless, the killing capacity and cytotoxicity of NK cells were stronger than those of the HC group. This may be associated with the increased activating receptors expression of NK cells. Conclusions This study demonstrated that the activating receptors expression and the cytotoxicity of NK cells in the blood were independent predictors of development in HCC patients, and the recovery of NKG2D+CD56dim NK cells could increase the prognostic value.