HLA antigen expression and malignant mesothelioma.
The expression of HLA antigens by a tumor may determine its progression and metastatic potential by influencing the immune response to that tumor. The upregulation of HLA antigen expression on some cell types by interferons (IFNs) may contribute to their antitumor activity. Malignant mesothelioma (MM) is a tumor that has a poor prognosis and is unaffected by conventional therapy, although immunotherapy has not been adequately assessed. In this study, we have examined the constitutive and IFN-inducible expression of class I and class II HLA antigens on MM cell lines using indirect immunofluorescence and Northern blotting. All MM cell lines constitutively expressed class I, but not class II, surface antigen, and all three class I loci (HLA-A, HLA-B, and HLA-C) were expressed. The MM cell lines were heterogeneous in their response to the IFNs. Treatment with IFN-alpha marginally increased class I surface expression, but not class II. Class I mRNA was, however, clearly increased in all cell lines after IFN-alpha treatment, suggesting that class I surface antigen was already maximally expressed. IFN-gamma increased class I mRNA expression in all but one cell line and induced DR expression on three of the cell lines. DQ-beta, but not DQ-alpha, mRNA was inducible in the same three cell lines, but DQ surface antigen was never demonstrable.(ABSTRACT TRUNCATED AT 250 WORDS)
Christmas
T I
TI
Department of Medicine, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands.
Manning
L S
LS
Davis
M R
MR
Robinson
B W
BW
Garlepp
M J
MJ
D015152:Blotting, Northern; D015139:Blotting, Southern; D002455:Cell Division; D002462:Cell Membrane / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005796:Genes; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008654:Mesothelioma / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D007370:Interferon Type I; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma