Specific activation of the non-classical class I histocompatibility HLA-G antigen and expression of the ILT2 inhibitory receptor in human breast cancer.
The HLA-G molecule is a non-classical HLA class I antigen selectively expressed by trophoblastic cells that invade the maternal decidua during human pregnancy. HLA-G is believed to contribute to tolerance of the semi-allogeneic fetus by inhibiting maternal immune responses. Similarly, HLA-G expression in tumour cells may favour their escape from host immune surveillance. This study investigated HLA-G expression in human mammary tumours. Immunohistochemical analysis of cryo-preserved and paraffin-embedded breast tissue biopsies, using two HLA-G-specific antibodies, revealed that unlike non-cancerous breast tissue in the vicinity of the tumour, 14 out of 36 breast cancer lesions selectively expressed HLA-G. HLA-G expression was significantly more frequent in lesions that were highly infiltrated by host immune cells, thus correlating HLA-G activation with inflammation. Further histological and double-staining immunofluorescence analysis attributed HLA-G expression mainly to tumour epithelial cells and to subsets of infiltrating CD68+ and CD8+ cells. RT-PCR analysis suggested that HLA-G was activated at the transcriptional level in breast tumours. The presence of ILT2 (Ig-like transcript 2) killing inhibitory receptors known to interact with HLA-G was also demonstrated in host immune cells that infiltrate breast cancer lesions. These results indicate that HLA-G is up-regulated at high frequencies in human breast cancer, where it may impair efficient anti-tumour immunity.
Lefebvre
Sophie
S
Service de Recherches en Hémato-Immunologie, DSV/DRM, CEA, Institut d'Hématologie, Hôpital Saint-Louis, Centre Hayem, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
Antoine
Martine
M
Uzan
Serge
S
McMaster
Michael
M
Dausset
Jean
J
Carosella
Edgardo D
ED
Paul
Pascale
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018270:Carcinoma, Ductal, Breast / Q000276:immunology*; D018275:Carcinoma, Lobular / Q000276:immunology; D018276:Carcinoma, Medullary / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D019139:Tumor Escape; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C105299:LILRB1 protein, human