title: Switch of HLA-G alternative splicing in a melanoma cell line causes loss of HLA-G1 expression and sensitivity to NK lysis.
abstract: Considerable information has been accumulated on HLA-G expression in tumor lesions in which HLA-G is viewed as a way to turn off anti-tumoral immunity. Nevertheless, there is little data concerning the mechanisms by which expression and function of HLA-G are regulated in malignant cells. Here, we have addressed these points by studying a melanoma cell line derived from a surgically-removed HLA-G-positive melanoma lesion. We show that HLA-G expression in melanoma cells can be regulated at the mRNA splicing level. Indeed, melanoma cells rapidly switched from cell-surface HLA-G1 to intra-cellular HLA-G2 expression. This mechanism restored tumor sensitivity to NK lysis. Moreover, switch from HLA-G1 to HLA-G2 was strong enough to prevent re-expression of immunoprotective HLA-G1 even following treatments with cytokines and DNA demethylating agent. Modulating HLA-G at the mRNA splicing level would be an efficient way of lifting in vivo HLA-G-mediated tumor immune escape.
authors.affiliation: Service de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint-Louis, IUH, Paris, France. freiss@dsvidf.cea.fr
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rouas-Freiss
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bruel
authors.forename: Catherine
authors.initials: C
authors.lastname: Menier
authors.forename: Céline
authors.initials: C
authors.lastname: Marcou
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Edgardo D
authors.initials: ED
authors.lastname: Carosella
mesh_terms: D017398:Alternative Splicing; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D006680:HLA Antigens / Q000502:physiology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D011971:Receptors, Immunologic / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019139:Tumor Escape
chemical_list: D016207:Cytokines; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D011971:Receptors, Immunologic