Fig. 1

General view of surface receptors between NK cell and tumor cell. The anti-tumor functions of NK cell depend on a suite of activating and inhibitory receptors which combined to ligands on tumor cell surface or regulatory cytokines. Dramatical changes of the interaction lead to NK cell dysfunction and then cause tumor escape and progression. Novel agents targeting these special interactions have been explored to augment NK cell-mediated killing effect and recruit them to boost anti-tumor immunity. (1) CD33 CAR molecule; (2) CD-16/IL-15/CD33 TriKE; (3) Anti-CD16/CD19 BiKE; (4) Anti-TIGIT mAb, such as Tiragolumab; (5) Anti-KIR mAb, such as Lirilumab; (6) Anti-PD-1 mAb, such as Pembrolizumab; (7) Anti-NKG2A mAb, such as Monalizumab. BAT-3, HLA-B associated transcript 3; BiKE, bispecific killer cell engager; B7-H6, B7 homolog 6; CAR, chimeric antigen receptor; CD, cluster of differentiation; DAP10, DNAX-activation protein 10; Fas, factor related apoptosis; FcRγ, fragment crystallizable receptor γ; HLA, human leukocyte antigen; ICB, immune checkpoint blockade; IFN-αR, interferon-α receptor; IFN-γ, interferon-γ; IL-R, interleukin receptor; LILRB1, leukocyte immunoglobulin-like receptor B 1; mAb, monoclonal antibody; MICA, human MHC-I chain-related A; MICB, human MHC-I chain-related B; NKG2A, natural killer group 2 member A; NKG2D, natural killer group 2 member D; NKp30, natural killer receptor protein 30; NKp44, natural killer receptor protein 44; NKp46, natural killer receptor protein 46; KIRs, killer cell Ig-like receptors; PD-1, programmed cell death 1; PD-L1, programmed cell death ligand 1; PD-L2, programmed cell death ligand 2; PGDF-DD, platelet derived growth factor DD; TGFβR, transforming growth factor-β receptor; TIGIT, T cell Ig and ITIM domain; TRAIL-R, TNF-related apoptosis inducing ligand-receptor; TriKE, trispecific killer cell engager; ULBPs, ULl6 binding proteins