Table 1.
Overview of the major NK cell receptors and Ligands involved in tumor cell recognition.
| NK Receptor | Ligand(s) | Ligand expression on tumor cells | References | |
|---|---|---|---|---|
| Inhibitory receptors | KIRs* | HLA-I (HLA-A,B,C) | Down-regulated in certain tumor cells | (50, 54) |
| CD94:NKG2A | HLA-E (non-classical HLA-I) | Down-regulated in certain tumor cells | (50, 54, 55) | |
| LILRB1 | HLA-I (HLA-A,B,C) | Down-regulated in certain tumor cells | (50, 54) | |
| HLA-G (non-classical HLA-I) | Up-regulated in certain tumors | (55–57) | ||
| Activating receptors | NKp46 | HSPG | Up-regulated/modified in different tumor cells | (58, 59) |
| Complement Factor P (properdin) | ? | (60) | ||
| Additional still unknown ligands** | (50, 61) | |||
| NKp44 | HSPG | Up-regulated/modified in different tumor cells | (58, 59) | |
| MLL5 isoform | Ectopically expressed at the cell surface of tumor cells of hematologic and solid tumors | (62) | ||
| PDGF-DD | Soluble factor released by several tumors (induces NKp44-dependent cytokine release) | (63) | ||
| Nidogen-1 | Decoy extracellular ligand expressed by different tumor cell lines (inhibits NKp44-dependent cytokine release) | (64) | ||
| NKp30 | HSPG | Up-regulated/modified in different tumor cells | (58, 59) | |
| BAT3 | Up-regulated in different tumor cells (released in exosomes) | (65) | ||
| B7-H6 | Highly expressed in different tumor cells | (66) | ||
| NKG2D | MICA/B, ULBP1-6 | Up-regulated in tumors of epithelial and non-epithelial origins | (67) | |
| DNAM-1 | CD155, CD112 | Up-regulated in many tumor cell types | (68) |
KIRs, Killer-cell immunoglobulin-like receptor; NKG2A, Natural Killer Group 2 A; LILRB1, Leukocyte Immunoglobulin Like Receptor B1; NKG2D, Natural Killer Group 2 D; DNAM-1, DNAX Accessory Molecule-1; HLA, Human Leukocyte Antigen; HSPG, Heparan Sulfate Proteoglycans; MLL5, mixed-lineage leukemia protein-5; PDGF-DD, platelet-derived growth factor—isoform dimer DD; BAT3, human leukocyte antigen (HLA)-B-associated transcript 3; MIC, MHC class I chain-related protein; ULBP, UL16 binding proteins.
Different tumor cell lines bind recombinant soluble NKp46 receptors and/or are killed by NK cells in a NKp46-dependent way but the putative ligand on these cells has not yet been identified.