title: Expression of LAG-3 is coincident with the impaired effector function of HBV-specific CD8(+) T cell in HCC patients.
abstract: Hepatitis B virus (HBV)-specific T cells play a key role in the pathogenesis of hepatocellular carcinoma (HCC), but little is known about the regulation of HBV-specific CD8(+) T cells function in HCC patients. Lymphocyte activation gene-3 (LAG-3) is an inhibitory molecule with diverse biologic effects on T cell function, including direct effects on CD8(+) T cells. In this study, we assessed the frequency and function of HBV-specific CD8(+) T cells derived from peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs) of HCC patients. Our data showed that compared with PBLs, LAG-3 expression is significantly up-regulated in tumor infiltrating CD8(+) T cells of HCC patients, and a severe functional defect were detectable in tumor infiltrating HBV-specific CD8(+) T cells at the tumor site. Since LAG-3 is an inhibitory molecule that plays a down-regulatory role on T cell responses, we found the correlation between LAG-3 expression and HBV-specific CD8(+) T cells dysfunction. Taken together, these results further provide a support for the role for LAG-3 in the suppression of HBV-specific cell-mediated immunity in HCC, and also provide a contribution to the potential cancer treatment.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Fu-Jun
authors.initials: FJ
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guang-Xin
authors.initials: GX
authors.lastname: Jin
authors.forename: Lei
authors.initials: L
authors.lastname: Yao
authors.forename: De-Quan
authors.initials: DQ
authors.lastname: Wu
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D012333:RNA, Messenger; D000093322:Lymphocyte Activation Gene 3 Protein