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.
Transforming growth factor-β (TGF-β) is a molecule with an extremely wide range of biological activities. In aqueous humor (AH) TGF-β is one of the factors involved in immunosuppression, and contributes to the immunological privilege of the anterior chamber of the eye. It may well be that ocular diseases, like corneal inflammation, disturb this immunological privilege by altering the cytokine equilibrium in AH. We compared the amounts of active, total, and the ratio active/total TGF-β in AH of patients with severe corneal disease leading to corneal transplantation with those values in patients with cataract. IL-6 levels in AH were determined too since raised levels may indicate intraocular inflammation. The aqueous humor samples were collected from patients with cataract undergoing cataract surgery and patients with corneal disease undergoing corneal transplantation. TGF-β(2) levels and IL-6 levels in AH were measured with a capture ELISA. TGF-β(2) in AH was mainly present as a latent complex. Eyes with corneal disease prior to corneal transplantation did not differ from eyes with cataract in the level of active, total, or the ratio active/total TGF-β(2) in AH. None of the eyes showed significant IL-6 levels. In both corneal disease and cataract the amounts of IL-6 and TGF-β(2) in AH thus suggest the presence of a normal immunological balance. This may have a positive influence on corneal graft survival. However, we observed raised levels of active TGF-β(2) in age-group 61-80 years, which might be related to the onset of cataract development.
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