Melanomas and melanoma cell lines do not express HLA-G, and the expressioncannot be induced by gamma IFN treatment

HLA-G is an effective ligand of natural killer (NK) inhibitory receptors, H LA-G transcripts have been detected in several human tumors, and cytokines like gamma interferon (IFN) enable HLA-G molecules to be expressed. These f indings are particularly upsetting in case of melanomas: IFN treatment is f requently included in melanoma therapeutic protocols, and downregulation of classical class I molecules occurs in nearly half of these tumors Therefor e, a melanoma cell downregulating classical class I and de novo expressing HLA-G, either constitutively or upon IFN treatment, is probably a stealthy target for the immune system, having inhibited both the cytotoxic T lymphoc yte (CTL) and the NK activity. To elucidate this point we have investigated the expression of HLA-G molecules in 45 melanoma cell lines before and aft er gamma IFN treatment. Analysis was performed by immunofluorescence and fl ow cytometry, using the anti-HLA-G MoAbs 87G and G233, by Western blot, usi ng the anti-HLA-G MEM/G1 MoAb and PAG1 antiserum, and by RT-PCR analysis In addition, 8 melanoma tissues from patients free from therapy and 6 nevi we re studied by immunohistochemistry using the 87G MoAb. No evidence was gath ered of HLA-G expression, neither constitutive nor, in cell lines, after ga mma IFN treatment. We therefore conclude that HLA-G expression is an uncomm on event in melanomas, and that a therapy including IFNs cannot harm the pa tient by inducing the de novo expression of HLA-G molecules at least in its G1 isoform.