Immunoregulation of intraocular tumours

Intraocular tumours reside within an organ that provides sanctuary from many immunological defence mechanisms. Antigens displayed on many intraocular tumours can elicit an aberrant systemic immune response in which systemic antigen-specific delayed-type hypersensitivity (DTH) is actively downregulated, thus denying the host one potential effector mechanism for controlling its intraocular tumour. Constituents within the aqueous humour inhibit the expression of DTH and natural killer cell effector mechanisms within the eye and thus protect intraocular tumours from immune-mediated rejection. Some experimental intraocular tumours in mice express potent tumour-specific antigens that stimulate the expansion of tumour-specific robust cytotoxic T lymphocyte (CTL) populations which enter the eye and mediate tumour rejection by piecemeal tumour necrosis. However, the presence of tumour-infiltrating lymphocytes (TIL) within an intraocular tumour does not inevitably lead to tumour resolution. In some cases CTL precursors infiltrate the intraocular tumour but fail to differentiate into mature cytolytic effector cells. Although uveal melanomas express melanoma-specific and melanoma-associated antigens that are capable of eliciting both humoral and cellular immunity, formidable barriers prevent the expression of tumour immunity. These barriers include: (a) anterior chamber-associated immune deviation; (b) in situ suppression of DTH effector cells; (c) suppression of natural killer cell activity in oculi; and (d) inactivation of the complement cascade by regulatory proteins expressed on uveal melanoma cells.