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


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).


CONCLUSIONS
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.
Lin
A
A
Medical Research Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical College, Linhai, Zhejiang, People's Republic of China.
Yan
W-H
WH
Xu
H-H
HH
Gan
M-F
MF
Cai
J-F
JF
Zhu
M
M
Zhou
M-Y
MY
D014408:Biomarkers, Tumor / Q000378:metabolism*; D001707:Biopsy, Needle; D002277:Carcinoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006680:HLA Antigens / Q000276:immunology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011379:Prognosis; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I