In particular, in various human cancer patient samples (including colon cancer, bladder cancer, and melanoma), a combination of IL-21 administration and PD-1/TIM3 therapy reinvigorate the functionality of PD-1+TIM3+ NK cells and overcome resistance to PD-1/TIM3 therapy (Seo et al., 2018). This evidence concerns the gene PDCD1 and melanoma.