Activating Natural Killer cell receptors (Activating NK receptors)

Activating Natural Killer (NK) cell receptors are a diverse group of germline-encoded surface proteins that trigger the effector functions of NK cells, including direct cytotoxicity and the production of inflammatory cytokines. These receptors, such as the Natural Cytotoxicity Receptors (NKp30, NKp44, NKp46), NKG2D, and CD16a (FcγRIIIa), allow NK cells to recognize and eliminate cells that are physiologically stressed, virally infected, or malignantly transformed. Unlike T-cell receptors, activating NK receptors do not require MHC-restricted antigen presentation, facilitating a rapid "natural" immune response. In many cancers, the expression of these receptors is downregulated, or their ligands are shed by tumor cells to evade immune detection. Therapeutic strategies are increasingly focused on harnessing these receptors through the development of NK cell engagers (BiKEs and TriKEs) and CAR-NK cell therapies, which aim to redirect and amplify NK cell-mediated anti-tumor activity.

Other names

NK cell activating receptorsKiller Activation ReceptorsKARsNatural Cytotoxicity ReceptorsNCRsNKG2DNKp30NKp44NKp46CD16aDNAM-1

NK cell engagement and activation via receptor agonism or bispecific/trispecific antibody-mediated redirection to tumor antigens.