HLA-G: a tolerance antigen implicated in tumor escape from immunosurveillance.

To define rational anti-tumor immunotherapy strategies, the reasons for the frequent lack of efficacy of the immune response to developing tumors must be elucidated. One hypothesis involves expression by tumor cells of molecu les with local immunosuppressive effects. HLA-G is known to be involved in tolerance of the fetus by the maternal immune system. We studied HLA-G expr ession in primary and metastatic melanomas (ex vivo biopsies and cell lines ). We found a high level of HLA-G transcription and expression at the surfa ce of the cells. A variety of patterns of HLA-G isoform transcription and p rotein expression were seen. The ability of HLA-G to inhibit the cytotoxic effect of two immunocompetent cell types involved in the antitumor response , namely natural killer cells (NK) and T-cells, suggests that HLA-G may hel p tumors evade the immune system.