It has been shown that Treg cells disproportionally accumulate in tumors as they increase in size or enter an advanced disease stage (228–232), that the response to anti-CTLA-4 therapy is reduced at increased tumor burdens (233, 234) and that overall survival following anti-PD-1 treatment in advanced melanoma varies negatively with baseline tumor size (235). This evidence concerns the gene PDCD1 and melanoma.