HLA-G expression in melanoma: a way for tumor cells to escape from immunosurveillance.
Considering the well established role of nonclassical HLA-G class I molecules in inhibiting natural killer (NK) cell function, the consequence of abnormal HLA-G expression in malignant cells should be the escape of tumors from immunosurveillance. To examine this hypothesis, we analyzed HLA-G expression and NK sensitivity in human malignant melanoma cells. Our analysis of three melanoma cell lines and ex vivo biopsy demonstrated that (i) IGR and M74 human melanoma cell lines exhibit a high level of HLA-G transcription with differential HLA-G isoform transcription and protein expression patterns, (ii) a higher level of HLA-G transcription ex vivo is detected in a skin melanoma metastasis biopsy compared with a healthy skin fragment from the same individual, and (iii) HLA-G protein isoforms other than membrane-bound HLA-G1 protect IGR from NK lysis. It thus appears of critical importance to consider the specific role of HLA-G expression in tumors in the design of future cancer immunotherapies.
Paul
P
P
Direction des Sciences du Vivant-Department de Recherche Medicale, Service de Recherches en Hemato-Immunologie, Commissariat à l'Energie Atomique, Hôpital Saint-Louis, Centre Hayem, 1, Avenue Claude-Vellefaux, 75010 Paris, France.
Rouas-Freiss
N
N
Khalil-Daher
I
I
Moreau
P
P
Riteau
B
B
Le Gal
F A
FA
Avril
M F
MF
Dausset
J
J
Guillet
J G
JG
Carosella
E D
ED
D002462:Cell Membrane / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers; D006680:HLA Antigens / Q000096:biosynthesis*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007157:Immunologic Surveillance / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I