Melanomas and melanoma cell lines do not express HLA-G, and the expression cannot be induced by γIFN treatment

HLA‐G is an effective ligand of natural killer (NK) inhibitory receptors, HLA‐G transcripts have been detected in several human tumors, and cytokines like γ interferon (IFN) enable HLA‐G molecules to be expressed. These findings are particularly upsetting in case of melanomas: IFN treatment is frequently included in melanoma therapeutic protocols, and downregulation of classical class I molecules occurs in nearly half of these tumors. Therefore, 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 lymphocyte (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 after γIFN treatment. Analysis was performed by immunofluorescence and flow cytometry, using the anti‐HLA‐G MoAbs 87G and G233, by Western blot, using 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 were studied by immunohistochemistry using the 87G MoAb. No evidence was gathered of HLA‐G expression, neither constitutive nor, in cell lines, after γIFN treatment. We therefore conclude that HLA‐G expression is an uncommon event in melanomas, and that a therapy including IFNs cannot harm the patient by inducing the de novo expression of HLA‐G molecules at least in its G1 isoform.