Exosomes bearing HLA-G are released by melanoma cells.
Tumor cells release membrane vesicles, named exosomes, capable of specific cytotoxic T-lymphocyte activation by transferring tumor antigens to dendritic cells. By contrast, the nonclassical human leucocyte antigen (HLA)-G class I molecule displays immunotolerant properties and can be ectopically expressed by tumor cells, thereby allowing their escape from immunosurveillance. We describe here that a melanoma cell line, named Fon, established from an HLA-G-positive melanoma biopsy, spontaneously expressed high levels of the HLA-G1 membrane-bound isoform. Exosomes released by Fon cells were purified and analyzed both for their density on sucrose gradient and their protein composition by Western blotting and flow cytometry. Besides the expression of well-described proteins such as Lamp-2, notably, these melanoma-derived exosomes bore HLA-G1. In addition, exosomes harboring HLA-G1 were secreted by the HLA-G-negative M8 melanoma cells transfected with the HLA-G1 cDNA. Thus, the presence of tolerogenic HLA-G molecules on melanoma-derived exosomes may provide a novel way for tumors to modulate host's immune response.
Riteau
Béatrice
B
Service de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint-Louis, IUH, Paris, France.
Faure
Florence
F
Menier
Catherine
C
Viel
Sophie
S
Carosella
Edgardo D
ED
Amigorena
Sèbastian
S
Rouas-Freiss
Nathalie
N
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology; D005434:Flow Cytometry; 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; D007157:Immunologic Surveillance; D008207:Lymphatic Metastasis; D051907:Lysosomal Membrane Proteins; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D022142:Secretory Vesicles / Q000276:immunology* / Q000378:metabolism; D060149:Tetraspanin 30; D014162:Transfection; D019139:Tumor Escape
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554586:CD63 protein, human; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D051907:Lysosomal Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30