While the link between upregulation of CD155 and tumor progression in GBM and other tumors has rendered CD155 a checkpoint target of potential interest, the related downregulation of DNAM-1 on NK cells in the TME within the context of CD155/TIGIT activity, coupled with its relatively lower affinity for CD155 and CD112 compared to that of TIGIT, limits NK cell activation and colors these pathways with additional complexity [40, 45]. This evidence concerns the gene CD226 and neoplasm.