T-cell recognition of melanoma-associated antigens

In this review, we summarize the significant progress that has been made in the identification of melanoma-associated antigens (MAA) recognized by cyt otoxic T-lymphocytes (CTL). These antigens belong to three main groups: tum or-associated testis-specific antigens (e.g., MAGE, BAGE, and CAGE); melano cyte differentiation antigens (e.g., tyrosinase, Melan-A/MART-1); and mutat ed or aberrantly expressed molecules (e.g, CDK4, MUM-1, beta-catenin). Alth ough strong CTL activity may be induced ex vivo against most of these antig ens, often in the presence of excess cytokines and antigen, a clear underst anding of the functional status of CTL in vivo and their impact on tumor gr owth, is still lacking. Several mechanisms are described that potentially c ontribute to tumor cell evasion of the immune response, suggesting that any anitumor efficacy achieved by immune effecters may be offset by factors th at result ultimately in tumor progression. Nevertheless, most of these MAA are currently being investigated as immunizing agents in clinical studies, the conflicting results of which are reviewed. Indeed, the therapeutic pote ntial of MAA has still to be fully exploited and new strategies have to be found in order to achieve an effective and long-lasting in vivo immune cont rol of melanoma growth and progression. (C) 2000 Wiley-Liss, Inc.