Tumor cell ligands for Natural Killer cell activating and inhibitory receptors (NK cell ligands)

Tumor cell ligands for Natural Killer (NK) cell activating and inhibitory receptors are a diverse group of surface proteins that regulate the immune system's ability to identify and destroy malignant cells. Activating ligands, such as MHC class I polypeptide-related sequence A and B (MICA/B) and UL16-binding proteins (ULBPs), bind to receptors like NKG2D to trigger NK cell cytotoxicity and cytokine release (PMID: 11777960). Conversely, inhibitory ligands, including HLA-E and various MHC class I molecules, bind to receptors like NKG2A and Killer-cell Immunoglobulin-like Receptors (KIRs) to provide inhibitory signals that prevent the destruction of healthy cells (PMID: 9486650). In many cancers, tumors evade immune surveillance by downregulating activating ligands or upregulating inhibitory ligands such as PD-L1 and CD155 (PMID: 27693132). Therapeutic interventions targeting these ligands, such as monoclonal antibodies or NK cell engagers, aim to disrupt inhibitory checkpoints or amplify activating signals to enhance the anti-tumor efficacy of the innate immune system (PMID: 30546055).

Other names

NK cell receptor ligandsNKR ligandsTumor-associated NK ligandsNKG2D ligandsCheckpoint ligands

Blocking inhibitory ligand-receptor interactions (checkpoint inhibition) or enhancing activating ligand-receptor signaling to restore and promote Natural Killer cell-mediated lysis of tumor cells.