CD4⁺ T cells play a critical role in the antitumor immune response by orchestrating both Th1 and Th2 effector mechanisms. While CD8⁺ T cells are traditionally considered the primary effector cells responsible for tumor killing, CD4⁺ T cells are essential for priming CD8⁺ T cells and for activating other immune cells, such as macrophages and eosinophils, which contribute to tumor destruction. Vaccination with irradiated tumor cells transduced to secrete granulocyte/macrophage colony-stimulating factor (GM-CSF) induces both Th1 and Th2 responses, which are necessary for maximal antitumor immunity. These responses involve the production of cytokines like γ-IFN and IL-4, which activate macrophages and eosinophils to produce reactive oxygen species and nitric oxide, leading to tumor cell death. CD4⁺ T cells also provide help for the activation and function of CD8⁺ T cells, which are critical for recognizing and killing tumor cells. However, CD4⁺ T cells also contribute directly to the effector phase of tumor rejection by recruiting and activating other immune cells. The study highlights the importance of both Th1 and Th2 cytokines in the antitumor immune response, as well as the roles of macrophages and eosinophils in tumor destruction. The findings suggest that CD4⁺ T cells are essential for the full antitumor immune response, and that their absence significantly impairs tumor rejection. The results also indicate that the antitumor immune response requires the coordinated action of multiple immune cells, including CD4⁺ and CD8⁺ T cells, macrophages, and eosinophils. The study underscores the importance of CD4⁺ T cells in orchestrating the immune response to tumors and highlights the potential of CD4⁺ T cell-based vaccines in cancer immunotherapy.CD4⁺ T cells play a critical role in the antitumor immune response by orchestrating both Th1 and Th2 effector mechanisms. While CD8⁺ T cells are traditionally considered the primary effector cells responsible for tumor killing, CD4⁺ T cells are essential for priming CD8⁺ T cells and for activating other immune cells, such as macrophages and eosinophils, which contribute to tumor destruction. Vaccination with irradiated tumor cells transduced to secrete granulocyte/macrophage colony-stimulating factor (GM-CSF) induces both Th1 and Th2 responses, which are necessary for maximal antitumor immunity. These responses involve the production of cytokines like γ-IFN and IL-4, which activate macrophages and eosinophils to produce reactive oxygen species and nitric oxide, leading to tumor cell death. CD4⁺ T cells also provide help for the activation and function of CD8⁺ T cells, which are critical for recognizing and killing tumor cells. However, CD4⁺ T cells also contribute directly to the effector phase of tumor rejection by recruiting and activating other immune cells. The study highlights the importance of both Th1 and Th2 cytokines in the antitumor immune response, as well as the roles of macrophages and eosinophils in tumor destruction. The findings suggest that CD4⁺ T cells are essential for the full antitumor immune response, and that their absence significantly impairs tumor rejection. The results also indicate that the antitumor immune response requires the coordinated action of multiple immune cells, including CD4⁺ and CD8⁺ T cells, macrophages, and eosinophils. The study underscores the importance of CD4⁺ T cells in orchestrating the immune response to tumors and highlights the potential of CD4⁺ T cell-based vaccines in cancer immunotherapy.