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Switch of HLA‐G alternative splicing in a melanoma cell line causes loss of HLA‐G1 expression and sensitivity to NK lysis
Author(s) -
RouasFreiss Nathalie,
Bruel Sylvie,
Menier Catherine,
Marcou Céline,
Moreau Philippe,
Carosella Edgardo D.
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21151
Subject(s) - human leukocyte antigen , rna splicing , cancer research , lysis , cell culture , melanoma , alternative splicing , cytolysis , hla g , biology , immunology , medicine , genetics , in vitro , antigen , gene , exon , cytotoxicity , rna
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. © 2005 Wiley‐Liss, Inc.