Epigenetically-regulated Tumor-Associated Antigens in melanoma

Surgical resection represents the treatment of choice for primary melanoma, providing the best results, in terms of long-term survival, for thin lesions. However, surgery has limited efficacy in the management of locoregional and distant metastases, as do chemotherapy and radiotherapy. In this context, immunotherapy is a promising and additional therapeutic option to cure melanoma patients and to prevent relapse of the disease. The identification and characterization of immunogenic tumor-associated antigens (TAAs) has prompted the design and development of a plethora of therapeutic vaccines to drive the host immune system to specifically recognize and eradicate neoplastic cells. Although encouraging, clinical results obtained with TAA-based vaccination are not yet satisfactory. In this regard, a great number of experimental data indicate that neoplastic cells are capable of escaping the host's immune surveillance and impairing the efficacy of immunotherapeutic approaches by different mechanisms. Among these, the epigenetic editing of gene-expression patterns by aberrant DNA hypermethylation and/or histone deacetylation is emerging as a frequent and important tool employed by melanoma cells to trigger the downregulation of the components of the tumor presentation/recognition complex. This review will summarize the available data derived from preclinical and clinical research using epigenetic drugs, such as histone deacetylase and DNA methyltransferase inhibitors, to revert epigenetic alterations, and the current knowledge of the potential immunotherapeutic implications of epigenetic treatment in the melanoma clinic. © 2009 Expert Reviews Ltd.