CD4 and neoplasm: Previously, we had observed that melanoma recurred about 50% of the time in this model.9,37 In these cases, the CD4+ T cells had become exhausted, expressing high amounts of PD-1, LAG-3, and TIGIT.9 Tumor-specific Tregs also increased in number and proportion during recurrence.9 Since NK1.1+ cell depletion has been shown to decrease chronic exhaustion of T cells,35 we wondered if NK1.1+ cell depletion would prevent exhaustion of CD4+ T cells and thus prevent recurrence.