Tumor-specific up-regulation of the nonclassical class I HLA-G antigen expression in renal carcinoma.
HLA-G is a nonclassical class I antigen mainly expressed at the maternofetal interface during pregnancy where it is thought to down-modulate maternal immune response against the semiallogeneic fetus. Recent studies indicate that ectopic up-regulation of HLA-G expression on melanoma cells may also favor their escape from antitumor immune response. HLA-G expression was here investigated on paraffin-embedded tumor and adjacent normal renal tissues of 18 renal cell carcinoma (RCC) patients. We provide evidence that HLA-G antigen is differentially expressed in carcinoma and normal renal cells and that up-regulation of this antigen in the tumor cells is more frequent than alterations of other MHC class I or class II antigens. We also demonstrated that HLA-G cell surface expression and secretion is maintained in a tumor cell line (DM) established from an HLA-G-positive RCC lesion. Furthermore, we show that type I (alpha and beta) and, in particular, type II (gamma) IFN treatment enhances steady-state mRNA levels and cell surface expression of HLA-G in the DM cell line. As several studies suggest that HLA-G displays various functional features that allow down-modulation of immune response in vitro, we propose that selective in vivo expression of HLA-G may participate in the impairment of antitumor immunity in RCC.
Ibrahim
E C
EC
CEA, Service de Recherches en Hémato-Immunologie, DSV/DRM, Hôpital Saint-Louis, Centre Hayem, 75010 Paris, France.
Guerra
N
N
Lacombe
M J
MJ
Angevin
E
E
Chouaib
S
S
Carosella
E D
ED
Caignard
A
A
Paul
P
P
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D007372:Interferons / Q000494:pharmacology; D007668:Kidney / Q000276:immunology; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D020033:Protein Isoforms; D012333:RNA, Messenger; D007372:Interferons