PDCD1 and neoplasm: Mutations in the immunoreceptor tyrosine-based inhibitory motif (ITIM, Y225F) and the immunoreceptor tyrosine-based switch motif (ITSM, Y248F) in the cytosolic tail of PD-1 expressed on melanoma cells decrease tumor growth, indicating that these ITIM and ITSM in PD-1 have an important role in regulating tumor cell-intrinsic PD-1-mediated tumorigenesis (Kleffel et al., 2015).