Abstract: Background and purpose: Programmed death 1 (PD-1) plays an important role in the regulation of peripheral immune tolerance. The expression of PD-1 in tumor-infiltrating lymphocytes of hepatocellular carcinoma (HCC) and the relationship between PD-1 expression and CD8 ⁺ T lymphocytes is unclear. This study was aimed to investigate the expression of PD-1 in tumor-infiltrating lymphocytes of HCC and its prognostic significance. Methods: Pathological paraffin samples of 344 HCC patients who underwent surgery in Nantong Third People’s Hospital from January 2008 to December 2016 were included. Tissue microarray was prepared. The protein expressions of PD-1 and programmed death ligand-1 (PD-L1) in HCC tissues were detected by immunohistochemical assay. Statistical analysis was performed to determine the correlation between the expression of PD-1 in tumor-infiltrating lymphocytes and the clinicopathological parameters of HCC, the expression of PD-L1, CD8 ⁺ T lymphocytes and the prognosis of patients. The influence of CD8 ⁺ PD-1 ⁺ double expression T lymphocyte density on the prognosis of HCC patients was detected by immunohistochemical double labeling. Results: PD-1 positive signal was localized on the membrane or cytoplasm of HCC tumor-infiltrating lymphocytes. The high expression rate of PD-1 was 43.9%, which was related to tumor histological grade (P=0.009), tumor cell PD-L1 expression (P<0.001), tumor-infiltrating lymphocytes PD-L1 expression (P<0.001) and tumor infiltrating CD8 ⁺ T lymphocyte density (P=0.003). Moreover, PD-1 overexpression was an independent risk factor for evaluating the overall survival (OS) rate and the disease-free survival (DFS) rate (OS: HR=1.654, P=0.010; DFS: HR=2.518, P<0.001). In addition, patients with high-density tumor-infiltrating CD8 ⁺ PD-1 ⁺ double expression T-lymphocytes had worse OS and DFS compared with those with low-density tumor (P<0.001). Conclusion: The expression of PD-1 in tumor-infiltrating lymphocytes of HCC may be a potential prognostic factor.

Key words: Programmed death 1, Programmed death ligand-1, Hepatocellular carcinoma, Prognosis