Prognostic Value Of Natural Killer Cells In Hepatocellular Carcinoma

BACKGROUND.Natural killer(NK) cells are a group of effector cells that act nonspecifically against tumor cells.The correlation between intratumoral or peritumoral NK cell infiltration and clinicopathologic features in HCC remains unclear.METHODS.The authors selected 240 patients with hepatocellular carcinoma who underwent hepatectomy at Zhongshan Hospital affiliated Fudan University between 2002-2006. Immunohistochemical staining with the CD57 antibody was performed for the evaluation of NK cell infiltration in HCC tissue microarray.For every patient,3 spots of tumor-containing tissue and 3 spots of peritumoral tissue containing CD57 positive cells were evaluated(the diameter of each spot is 1 mm)and the number of NK cells were counted(magnification,400).The patients were first divided into 2 groups as the median number of NK cells:patients with a higher level of intratumoral NK infiltration(n=118)(＞15.00 NK cells/spot average) and patients with a lower level of intratumoral NK infiltration(n=122)(≤15.00 NK cells/ spot average).Then according to peritumoral NK infiltration,all patients were classified into a higher infiltrating group(n = 120)(＞24.17 cells/spot average) and a lower group(n = 120) (≤24.17 cells/spot average).The Kaplan-Meier curve was used to analyze surgical outcome.Multivariate analyses were performed to evaluate prognostic factors.RESULTS.On univariate analysis,patients with a higher level of intratumoral NK infiltration didn't have a prolonger disease-free survival(DFS)(P =0.102) than patients with a lower level of NK infiltration,but had a significant prolonger overall survival(OS)(P =0.018).Higher level of peritumoral NK infiltration correlated either with prolonged DFS or OS.Intratumoral NK cell infiltration was found to correlate to none of the considered clinicopathologic features.Peritumoral NK cell infiltration was found to correlate to liver cirrhosis.There was no correlation between intratumoral and peritumoral NK cells infiltration(P = 0.050;correlation coefficient 0.126).The 3-year survival rate of patients with a higher rate of intratumoral NK infiltration was 62%, which was better than 46%of patients with a lower level of intratumoral NK infiltration(P =0.018).Multivariate analysis showed intratumoral NK cell infiltration to be a significant independent prognostic factor.(P =0.036;hazard ratio 1.61). Especially among the tumor thrombus positive group,patients with a high level of intratumoral NK infiltration did have a prolonger disease-free survival(DFS)(P =0.013) and a prolonger overall survival(OS)(P =0.009) than patients with a low level of intratumoral NK infiltration.CONCLUSIONS.Patients with a higher level of intratumoral NK infiltration were found to have a better prognosis than those with a lower level of NK infiltration,which is obvious among the the tumor thrombus positive patients,and may suggest a potential role in the treatment of patients with hepatocelluar carcinoma.The potential application of this work.Intratumoral NK infiltration in HCC tissue have correlated to a better postoperative prognosis,which proved the potential of NK immunotherapy for better control of HCC.The novelty of this work.For the first time,in a large cohort of patients,we demonstrated that tumor-infiltrating NK may be of prognostic value in HCC following resection.