HLA expression in uveal melanoma: there is no rule without some exception

A decrease in the expression of HLA antigens is considered a characteristic of tumor progression and is considered an important tumor-escape mechanism. In general, HLA Class I expression is even further decreased on metastases. Tumor cells that loose their HLA Class I antigens become less susceptible to lysis by specific T cells, but may become more sensitive to Natural Killer cells. Loss of HLA Class I can be observed at different levels, i.e. total loss of Class I, loss of expression of one locus or one haplotype, or even one specific allele. We studied HLA expression on human uveal melanoma and observed that loss of expression of a locus or one or more alleles is a common phenomenon. However, in contrast with the commonly accepted paradigm, loss of HLA Class I expression on the uveal melanoma was not associated with tumor cell escape and a worse survival, but with a better survival of the patients involved. We hypothesize that this is due to the route of metastases formation: in uveal melanoma, spreading of metastases is purely hematogeneous, and it is quite possible that NK-cell mediated surveillance of tumor cells in the blood is the underlying mechanism. This is supported by our finding that metastases of uveal melanoma have a high HLA Class I expression, leading to our conclusion that uveal melanoma is an exception to the general rule regarding HLA Class I expression in tumor immunology.