Differential in vivo and in vitro HLA-G expression in melanoma cells: potential mechanisms.

The potential role of human leukocyte antigen G (HLA-G) in tumor immune escape has stimulated interest in the analysis of the expression of this molecule in malignant cells. In melanoma approximately 30% and less than 1% of surgically-removed lesions and cultured cell lines, respectively, have been found to express HLA-G protein. The reason for the marked difference in HLA-G expression frequency is unknown. Here we discuss the potential role of HLA-G detection methodology, stress factors in the tumor microenvironment, and epigenetic changes during tumor progression in the differential in vivo and in vitro HLA-G expression in melanoma cells. We propose a model that may account for the preferential in vivo HLA-G expression in melanoma cells. If proven correct, this model represents a useful background to investigate the mechanisms regulating HLA-G expression in melanoma cells and to devise strategies to counteract HLA-G expression in patients with melanoma.