High frequency of allele‐specific down‐regulation of HLA class I expression in uveal melanoma cell lines

Uveal melanoma is the most common primary intra‐ocular tumor in adults and has a high mortality rate due to liver metastases, for which no effective treatment is available. To investigate whether immunotherapy might be feasible in uveal melanoma, the HLA class I surface expression of 6 uveal melanoma cell lines was analyzed by flow cytometry using a broad panel of allele‐specific monoclonal antibodies. To up‐regulate HLA expression, cells were also cultured with IFN‐α or ‐γ . In general, expression of HLA‐A alleles was high (except for cell line EOM‐3) and could be further up‐regulated by both IFN‐α and ‐γ. In cell line EOM‐3, IFN‐γ treatment resulted in significant HLA‐A expression while IFN‐α treatment did not. Expression of HLA‐B alleles was low or even negative. Variable effects were observed after IFN treatment. In 3 cell lines, expression of some HLA‐B alleles could not be induced by IFN‐α or ‐γ: HLA‐B44 in cell line 92–1, HLA‐B15 in cell line OCM‐1 and HLA‐B5 in cell line MEL‐202. The other B alleles of these cell lines showed enhanced expression levels upon IFN stimulation. In OMM‐1 cells, IFN‐α and ‐γ increased the expression of HLA‐A but did not induce expression of the 2 B alleles, indicating an HLA‐B locus–specific loss. We thus found a high frequency of allele‐specific and locus‐specific down‐regulation of HLA expression in uveal melanoma cell lines. Some of these defects were not restored by IFN‐α or ‐γ treatment. The lack of HLA expression may explain why uveal melanoma cells escape immune surveillance by cytotoxic T cells and complicate the development of immunotherapy in uveal melanoma. Int. J. Cancer 85:697–702, 2000. © 2000 Wiley‐Liss, Inc.