[Potential endogenous immunological self-protection of uveal melanoma by indoleamine 2,3-dioxygenase]

Uveal melanomas are the most common intraocular tumours in the adult. Although they represent less than 1% of all tumour cases, uveal melanomas are considerd to be rather aggressive due to early hepatic metastases. Indoleamine 2,3-dioxygenase (IDO) is the principle enzyme in the degradation of the essential amino acid L-tryptophan to L-kynurenine.

In this study, the L-kynurenine production of six uveal melanoma cell lines was examined and immunohistochemistry performed for detection of IDO expression within uveal melanomas.

In all the examined cell lines, a basal degradation of tryptophan to L-kynurenine was detectable. Supplementation with interferon-gamma could up-regulate this basal L-kynurenine production. The expression of IDO using immunohistochemistry was demonstrated within all examined tumours.

The expression of IDO within the tumours may shed light on an important adaptive mechanism which allows the melanoma cells to escape T-cell-dependent immunosurveillance as soon as these cells metastise and enter non-immunologically privileged tissue. As competitive inhibition of IDO by 1-methyl-tryptophan is possible, a new therapeutic pathway might be available.