Summary: The importance of T-cell-mediated antitumor immunity has been demonstrated in both animal models and human cancer therapy. The identification of major histocompatibility complex (MHC) class I-restricted tumor antigens has generated a resurgence of interest in immunotherapy for cancer. However, recent studies suggest that therapeutic strategies that have mainly focused on the use of CD8+ T cells (and MHC class I-restricted tumor antigens) may not be effective in eliminating cancer cells in patients. Novel strategies have been developed for enhancing T-cell responses against cancer by prolonging antigen presentation of dendritic cells to T cells and the inclusion of MHC class II-restricted tumor antigens. identification of MHC class II-restricted tumor antigens, which are capable of stimulating CD4+ T cells, not only aids our understanding of the host immune responses against cancer antigens, but also provides opportunities for developing effective cancer vaccines.