Increased PD-1 and decreased CD28 expression in chronic hepatitis B patients with advanced hepatocellular carcinoma.

ABSTRACT

BACKGROUND/AIMS: Hepatitis B infection is a well-known cause of hepatocellular carcinoma (HCC). This study aims to investigate the role that the co-stimulatory molecule CD28 and co-inhibitory molecule programmed death-1 (PD-1) play in compromising the function of tumour-infiltrating lymphocytes (TIL) in hepatitis B virus (HBV)-related HCC. METHODS: A total of 45 patients with HBV-related HCC were enrolled during the period February 2008 to March 2010. The immune phenotype and the expression of PD-1, CD28 and CD127 in TIL in biopsy specimens and in peripheral blood lymphocytes (PBL) from the same patients were analysed by flow cytometry. RESULTS: Among the 45 patients, there was a male predominance (80%) and the mean age was 50 ± 13.68 years (range 29-71). The majority of TIL were CD45RO(+) CD69(+). PD-1 expression was higher and CD28 and CD127 expression levels were lower in TIL than in PBL. The prevalence of portal vein thrombosis was 40%. Furthermore, tumour thrombosis invasion into the portal vein correlated with the expression level of the PD-1 co-inhibitory molecule. CONCLUSION: PD-1(+) tumour-infiltrating lymphocytes correlate with portal vein thrombosis and might serve as a potential prognostic marker of and a novel therapeutic target for HBV-related HCC.