A recent report showed that, in PBMC isolated from advanced melanoma patient, a fraction of PD-1+ NY-ESO-1–specific CD8+ T cells co-expressed TIM-3 and PD-1 and these cells were more dysfunctional than TIM-3−PD-1+ and TIM-3−PD-1− counterparts [4]. The gene discussed is CD8A; the disease is melanoma.