Moreover, the combination of the CD96 blockade strategy with anti-CTLA-4 and anti-PD-1 immunotherapy demonstrated more significant effects to facilitate the infiltration of NK cells into tumor mass [120, 126], which ultimately indicates that targeting of the CD96 checkpoint on NK cells might provide a potential immunotherapy strategy to enhance NK cells-mediated anti-tumor efficacy [127]. This evidence concerns the gene CD96 and neoplasm.