Expression of LAG-3 is coincident with the impaired effector function of HBV-specific CD8(+) T cell in HCC patients

Immunol Lett. 2013 Feb;150(1-2):116-22. doi: 10.1016/j.imlet.2012.12.004. Epub 2012 Dec 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / metabolism*
  • Case-Control Studies
  • Female
  • Gene Expression
  • Hepatitis B virus / immunology*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / metabolism*
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Antigens, CD
  • CD223 antigen
  • RNA, Messenger