Dual role of B7-H6 as a novel prognostic marker in hepatocellular carcinoma.

B7 homolog 6 (B7-H6), a new member of the B7 family, is identified as an activating ligand for cytotoxicity triggering receptor 3 (NKp30) expressing on natural killer cells. The purpose of this study was to investigate the clinical significance of B7-H6 in hepatocellular carcinoma (HCC). We evaluated B7-H6 expression by immunohistochemistry in a cohort of 90 HCC tumors with clinical follow-up, the potential relationship between the B7-H6 expression and the clinicopathological characteristics of HCC patients was also analyzed. Stable B7-H6 knockdown in hepatoma cell line was established to explore the function and mechanism of B7-H6 in HCC. This study showed that high expression of B7-H6 was significantly associated with smaller tumor size, single tumor number in HCC, but no significant association was found between B7-H6 overexpression and other clinicopathological parameters. Moreover, Kaplan-Meier survival analysis showed that high expression of B7-H6 was significantly correlated with better survival of HCC patients. Knockdown of B7-H6 inhibited tumor cell proliferation and induced cell apoptosis. However, it also impaired the sensitivity of tumor cells to NK-mediated lysis together with significantly decreased degranulation and IFN-γ release of NK cells. These results indicated that B7-H6 has a dual role in HCC. It could be an independent indicator for better survival of HCC and maybe a potential target for future cancer treatment.