Clinical Significance Of PD-1 In Human Hepatocellular Carcinoma

Objective:1.To investigate the clinical significance of PD-1 on peripheral blood CD8~+ T lymphocytes in patients with HBV-related hepatocellular carcinoma(HCC).2.To reveal the relationship between the expression of PD-1/PD-L1 and the tumor microenviroment in patients with HCC.Method:1.Total of 66 untreated patients with HBV-related HCC were divided into 4 groups according to Barcelona clinic liver cancer staging classification(BCLC), 20 patients were of early stage,16 of intermediate stage,19 of advanced stage and 11 of terminal stage.The frequency of PD-1 on peripheral blood CD8~+T lymphocytes were detected respectively.Serum levels of fibrinogen(FIB), alpha-fetoprotein(AFP),HBVDNA,ALT and AST were detected also.2.Immunohistochemistry was employed to detect the expression of PD-1 /PD-L1 and CD8~+ T lymphocytes in normal liver,liver cirrhosis,and HCC tissues.Results:1.The frequency of PD-1 on peripheral blood CD8~+T lymphocytes increased significantly in HCC patients.It remarkably correlated with BCLC,weakly correlated with serum levels of FIB,ALT and AST,but had no statistical correlations with Child-pugh class,sex,age,HBVDNA and AFP.2.Both the expression of PD-1 and PD-L1 increased in HCC tissue compared with normal liver and liver cirrhosis tissues.Most CD8~+ T lymphocytes expressed PD-1 in HCC sections.CD8 and PD-L1 double staining show that few CD8~+ T lymphocytes could infiltrate into the tumor nodules,which highly expressed PD-L1.Conclusion: The level of PD-1 on peripheral blood CD8~+T lymphocytes were positively related to the progression of HCC,and could be a more promising prognostic marker for HCC,compared with FIB and AFP.Furthermore, immunohistochemistry results showed that PD-1/PD-L1 pathway played an important role in tumor immune evasion and provide the rationale for developing a novel immunotherapy of targeting the PD-1/PD-L1 pathway against this fatal malignancy.