Natural killer cell activating and inhibitory receptors (NKRs)

The term "Tumor and stressed cells recognized via NK activating/inhibitory receptors" refers to a biological pathway and a collective group of receptors that govern Natural Killer (NK) cell surveillance [1][2]. NK cells utilize a sophisticated "rheostat" system of activating and inhibitory receptors to distinguish between healthy, stressed, and malignant cells [2][4]. Inhibitory receptors, such as Killer-cell Immunoglobulin-like Receptors (KIRs) and NKG2A, typically recognize MHC class I molecules on healthy cells to prevent autoimmunity [2]. Conversely, activating receptors like NKG2D and Natural Cytotoxicity Receptors (NCRs) detect ligands that are upregulated during cellular stress, viral infection, or oncogenic transformation [2][3]. In the context of cancer, tumors often evade this system by downregulating activating ligands or overexpressing inhibitory ligands [3]. Therapeutic strategies targeting this system include monoclonal antibodies that block inhibitory checkpoints (e.g., NKG2A, KIR) or bispecific engagers that bridge NK cells to tumor antigens to restore the immune system's ability to eliminate tumor cells [3][4]. Sources: [1] Reactome Pathway Database (R-HSA-198933); [2] Vivier, E., et al. (2008) Nature Immunology; [3] Shimasaki, N., et al. (2020) Nature Reviews Drug Discovery; [4] Long, E. O., et al. (2013) Annual Review of Immunology.

Other names

NK cell receptorsNatural killer cell receptorsNK activating and inhibitory receptorsTumor and stressed cells recognized via NK activating/inhibitory receptors

Enhancement of NK cell-mediated cytotoxicity by blocking inhibitory receptor-ligand interactions (checkpoint blockade) or by directly stimulating activating receptors to promote the lysis of tumor and stressed cells.