Effects of interferon alfa and gamma on human uveal melanoma cells in vitro.

Abstract

Background-Uveal melanoma is a tumour with a high incidence of metastasis and a high mortality rate. Additional therapies to obtain a better local control or an effective treatment ofmetastases are necessary. Interferons may be applied. Methods (Br_J Ophthalmol 1995; 79: 847-855) In recent years the anti-tumour activities of interferons (IFNs) have been studied extensively. Promising therapeutic results have been reported, especially in the treatment of haematological malignancies. 1-3 IFNs may also be of importance in the therapy of high risk cutaneous melanoma4 5 although the results are variable. However, the exact mechanisms of the anti-tumour activities of IFNs (immunomodulatory or antiproliferative) are still unknown and it is impossible to predict which patients may benefit most from IFN treatment. With regard to the potential immunomodulatory effect, IFNs are able to modulate the expression of cell surface molecules such as HLA class I and class II antigens.6 These molecules are essential in the generation and regulation of an effective antitumour immune response by T cells, since tumour specific antigens can only be recognised by T lymphocytes when the antigens are presented in the groove of HLA molecules. Since allele specific binding of tumour specific antigens has been reported -for example, for human cutaneous melanoma,7-9 differences in the level of different HLA molecules might be important in the development of effective antitumour immune responses.In a previous study, we determined the expression of HLA class I and II antigens on frozen tissue sections of uveal melanoma. Differences in the level of expression of different HLA molecules were observed: HLA-B antigens showed a lower level of expression than HLA-A.10 This low level of allele specific HLA class I expression might effect a putative anti-tumour immune response in vivo. Based on these results we hypothesised that HLA molecules on uveal melanoma cells in vitro might be sensitive to IFN mediated upregulation of expression.

Metastatic Uveal Melanoma Therapy

“…In contrast to in vitro data that suggested activity of interferon alfa on human uveal melanoma cell lines, 53 immunotherapy with interferon administered alone or with interleukin-2 in 21 patients resulted in only 2 minor responses. 31 We observed no responses with interferon alfa-2b administered by hepatic arterial infusion to 16 patients with metastatic choroidal melanoma confined to the liver.…”

Metastatic uveal melanoma

“…Biochemotherapy has had limited evaluation for efficacy against metastatic uveal melanoma. In contrast to in-vitro data which suggests that interferon-a has an action on human melanoma cell lines [14], immunotherapy with interferon-a-2b administrated alone or with interleukin-2 has shown only few minor responses [15]. The experience with cutaneous melanoma has shown that biochemotherapy is superior to chemotherapy alone with regard to response rate and progression-free survival but with similar overall survival and higher toxicity [16].…”

Decitabine Up-regulates S100A2 Expression and Synergizes with IFN-γ to Kill Uveal Melanoma Cells

“…Several papers have shown that type I and type II IFNs can have variable effects on cell proliferation and integrin/adhesion molecule expression in uveal melanoma (12,13). Like cutaneous melanoma, the biology of uveal melanoma can also be affected through decitabine-induced gene re-expression.…”