CD226 and cancer: Indeed, co-activator 2B4, which synergizes with NKG2D, can also synergize with DNAM-1, but not simultaneously.258,259 These findings have profound implications for cancer immunotherapy aiming to exploit NKG2D and DNAM-1 and suggest that it is better to combine each one of them with other modalities, such as immune checkpoints, especially in the case of loss of expression of one of them.262–264