HLA-G expression in human melanoma cells: protection from NK cytolysis.
Expression of the non-classical HLA-G class I antigen is physiologically restricted to a limited number of tissues including trophoblasts, and is thought to play a role in establishing tolerance of the fetus by the maternal immune system. We investigated whether ectopic expression of HLA-G could also be detected in tumor cells and confer them the ability to escape immune cytotoxic responses. High levels of all alternatively spliced HLA-G transcripts could be detected in melanoma cells by RT-PCR. Analysis of biopsies from a melanoma patient revealed a higher HLA-G transcription level in skin metastasis as compared to healthy skin, while specific amplification of the HLA-G5 transcript was only observable in the tumor. HLA-G protein expression could also be detected in two melanoma cell lines. HLA-G-positive tumors inhibit cytotoxic lysis by the NK cell line YT2C2-PR. This inhibition is not observed with B-EBV cell lines bearing matched class I specificities, and is thought to occur through interaction of HLA-G with inhibitory receptors that are distinct from known KIRs interacting with HLA-E or classical class I molecules. Together, these results confirm that HLA-G expression at the surface of tumor cells can participate in the evasion of antitumoral immune responses and favor tumor progression.
Adrián Cabestré
F
F
CEA, Service de Recherches en Hémato-immunologie, DSV/DRM, Hôpital Saint-Louis, Paris, France.
Moreau
P
P
Riteau
B
B
Ibrahim
E C
EC
Le Danff
C
C
Dausset
J
J
Rouas-Freiss
N
N
Carosella
E D
ED
Paul
P
P
D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015870:Gene Expression; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger; D012867:Skin / Q000276:immunology / Q000473:pathology; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger