It has long been recognized that profound lymphodepletion prior to ACT increases the efficacy of therapy.22,23 This effect has been attributed to the elimination of suppressor cells and cytokine sinks as well as enhanced activation and availability of APCs.47 Herein, we have described how depletion of NK1.1+ cells enhances the rejection of established melanoma by adoptively transferred TRP-1-specific CD4+ T cells. This evidence concerns the gene CD4 and melanoma.