Interactions between immune checkpoint receptors and their cognate ligands. NK cells express multiple immune checkpoint receptors, which can interact with their cognate ligands on tumor cells as well as other immune cells, in particular, dendritic cells and Tregs. The red circles represent immune checkpoint receptors while the blue circles represent the ligands. SIGLEC7 and SIGLEC9 have common ligands that are sialic acids. The pink squares represent the classical ITIM motif and the light blue squares represent the ITSM motif, which have been implicated in mediating inhibitory signals. The light green squares represent the ITT-like motif. Cytoplasmic domains of other immune checkpoint receptors contain fewer known motifs (not marked as squares). CD73 is a nucleotidase, which does not have conventional inhibitory signaling domains. The black lines indicate receptor-ligand interactions.