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


CONCLUSIONS
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.
Hsu
Ping-Ning
PN
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yang
Tsuey-Ching
TC
Kao
Jung-Ta
JT
Cheng
Ken-Sheng
KS
Lee
Yi-Ju
YJ
Wang
Yuan-Min
YM
Hsieh
Chin-Tung
CT
Lin
Cheng-Wen
CW
Wu
Yi-Ying
YY
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D018106:CD28 Antigens; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor