CD8+ cytotoxic T-lymphocytes are major effector cells involved in immunologically specific tumor destruction in vivo, and CD4+ T-cells are essential for controlling this CD8+ T-cell-dependent tumor eradication. The presence of CD4+ T-cells with distinct functional roles has been recognized. The further understanding of the complexity of antitumor immune responses by CD4+ T-cells may be crucial for designing more effective cancer vaccines.