T cell-mediated immune responses in melanoma: implications for immunotherapy

In the last few years, a great deal of efforts have been directed towards understanding the molecular basis of T cell-mediated anti-tumor immunity and elucidating the molecular nature of tumor antigens recognized by T cells. Identification of a number of major histocompatibility complex (MHC) class I-restricted melanoma antigens has led to clinical trials aimed at developing effective cancer vaccines. These studies showed some evidence of therapeutic effect on the treatment of cancer, but the exclusive use of CD8+ T cells may not be effective in eradicating tumor. This rekindles interest in the role of CD4+ T cells in antitumor immunity, which play a central role in orchestrating the host immune response against cancer. Thus, we have attempted to identify MHC class II-restricted tumor antigens recognized by tumor-specific CD4+ T cells. The identification of tumor rejection antigens provides new opportunities for the development of therapeutic strategies against cancer. This review will summarize the current status of MHC class I and class II-restricted human tumor antigens, and their potential application to cancer treatment.