Switch of HLA-G alternative splicing in a melanoma cell line causes loss of HLA-G1 expression and sensitivity to NK lysis.
Int J Cancer
; 117(1): 114-22, 2005 Oct 20.
Article
in En
| MEDLINE
| ID: mdl-15880415
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skin Neoplasms
/
Killer Cells, Natural
/
Histocompatibility Antigens Class I
/
HLA Antigens
/
Melanoma
Type of study:
Diagnostic_studies
/
Etiology_studies
Limits:
Humans
Language:
En
Journal:
Int J Cancer
Year:
2005
Document type:
Article
Affiliation country:
France