CD226 and neoplasm: In the tumor microenvironment, NK cells transform to become dysfunctional cells with enhanced expression of inhibitory immune checkpoints, including the non-HLA-class I-specific inhibitory receptors (such as PD-1, TIGIT, CD112R, CD96, IL-1R8, and TIM-3) and HLA-class I-specific inhibitory receptors (such as KIR, NKG2A, and LAG-3), as well as decreased expression of activating receptors (such as NKG2D and CD226).