Switch of HLA-G alternative splicing in a melanoma cell line causes loss of HLA-G1 expression and sensitivity to NK lysis

✍ Scribed by Nathalie Rouas-Freiss; Sylvie Bruel; Catherine Menier; Céline Marcou; Philippe Moreau; Edgardo D. Carosella

• Book ID: 102272632
• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: French
• Weight: 379 KB
• Volume: 117
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.21151

✦ Synopsis

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.