The non-classical class I antigen HLA-G has been shown to play a role in fo
eto-maternal tolerance. It interacts with inhibitory receptors to down-regu
late natural killer and T cell cytotoxic functions. We here report our inve
stigations on HLA-G expression in melanoma cells and its implication in the
induction of immune tolerance to tumours. We provide the first evidence th
at both malignant human melanoma cell lines and ex vivo biopsies can exhibi
t high levels of HLA-G transcription with differential HLA-G isoform. trans
cription and protein expression patterns. We further demonstrated that mela
noma cells that express HLA-G inhibit NK cytolysis. We thus propose that HL
A-G expression may impede the elimination of malignant cells by anti-tumour
immune effector cells, constituting a newly described mechanism by which t
umour cells may evade immunosurveillance.