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.