HLA-G expression in human ovarian carcinoma counteracts NK cell function

Ann Oncol. 2007 Nov;18(11):1804-9. doi: 10.1093/annonc/mdm356. Epub 2007 Sep 9.

Abstract

Background: Human leukocyte antigen-G (HLA-G) is an important immunotolerant which could be a part of the strategies applied by malignant cells applied to avoid host immunosurveillance. Aberrant expression of HLA-G has been found in ovarian carcinoma. The aim of this study was to evaluate the HLA-G expression in ovarian cancer tissues and to explore its function in vitro.

Materials and methods: HLA-G expression in 33 primary ovarian carcinoma tissues was analyzed using immunohistochemistry with the anti-HLA-G monoclonal antibody (mAb) 4H84. Furthermore, the function of HLA-G in NK cell cytotoxicity was determined in vitro by cloning and expression of HLA-G on the ovarian carcinoma cell OVCAR-3.

Results: HLA-G expression was detected in 22/33 (66.7%) primary tumor tissues, but was absent in normal ovarian tissues (P<0.01). Cytotoxicity studies showed that HLA-G expression dramatically inhibits cell lyses by NK-92 cells (P<0.01), which could be restored by the anti-HLA-G conformational mAb 87G (P<0.01).

Conclusion: HLA-G was expressed in a significant number of primary ovarian carcinoma tissues, and HLA-G expression in OVCAR-3 could directly inhibit NK-92 cell lysis. Taken together, our results indicated that expression of HLA-G plays an important role in evasion of ovarian cancer cells from host immunosurveillance.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Biopsy, Needle
  • Carcinoma / genetics
  • Carcinoma / immunology*
  • Carcinoma / pathology
  • Case-Control Studies
  • Female
  • Gene Expression Regulation, Neoplastic
  • HLA Antigens / immunology*
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Immunohistochemistry
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / physiology*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Sensitivity and Specificity
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I