Enhanced tumor antigen–specific CTL response is generated by cross talk between NK cells, DCs, and CD8⁺ T cells and reduction in CD4⁺CD25⁺ T regulatory (T_reg) cell numbers at the priming site. Immunization strategies that trigger the innate and adaptive arms of the immune system and reduce the number of T_reg cells generate a more effective tumor antigen–specific CTL response (left panel) than those that trigger only the adaptive arm of the immune system (right panel).