Besides its tumor-intrinsic roles, PVR participates in multiple immunoregulatory events through finely tuned interaction with the stimulatory receptor DNAX accessory molecule 1 (DNAM-1, also known as CD226) and the inhibitory receptors T cell immunoreceptor with Ig and ITIM domains (TIGIT) and CD96 (32–34). This evidence concerns the gene TIGIT and neoplasm.