HLA-G in skin cancer: a wolf in sheep's clothing?

Despite well-defined and immunogenic tumor antigens, and even in the presence of tumor antigen-specific cytotoxic cells, the immune system does not appear to be very effective in eradicating cells that have undergone malignant transformation. Tumor cells, even though invading and representing a threat, are not truly "foreign" but autologous cells that have become transformed in a subtle way, enabling them to escape the host immune system. Melanoma, and to less extent nonmelanoma, skin cancers have developed different strategies to circumvent host immunosurveillance. HLA-G is one of the molecules implicated in cancer immunescape. This review will concentrate on induction and expression of this nonclassical class I molecule in different skin cancer types presenting existing experimental evidence on this topic.