Natural Killer cell surface receptors and tumor-associated ligands (NK receptors and ligands)

Natural Killer (NK) cell surface receptors and their tumor-associated ligands constitute a complex regulatory network essential for immune surveillance and the elimination of transformed cells (Vivier et al., 2018, Nature). Activating receptors, such as NKG2D, CD16 (FcγRIIIa), and the natural cytotoxicity receptors (NCRs), recognize stress-induced ligands or antibody-coated cells to trigger cytolytic activity and cytokine production (Shimasaki et al., 2020, Nature Reviews Drug Discovery). Conversely, inhibitory receptors like NKG2A and Killer cell Immunoglobulin-like Receptors (KIRs) recognize MHC class I molecules to prevent the destruction of healthy self cells (Long et al., 2013, Annual Review of Immunology). In many cancers, the balance of these signals is disrupted, allowing tumors to evade the immune system by shedding activating ligands or overexpressing inhibitory ones (Demaria et al., 2019, Nature Reviews Cancer). Therapeutic interventions targeting this axis include checkpoint inhibitors that block inhibitory signals, such as Monalizumab, and multi-specific NK cell engagers like AFM13 that physically link NK cells to tumor antigens (Kerbauy et al., 2021, Frontiers in Immunology). These therapies aim to restore or amplify the NK cell-mediated anti-tumor response, offering a promising alternative or complement to T-cell-based immunotherapies.

Other names

NK cell activating receptorsNK cell inhibitory receptorsNK cell engager targetsTumor-associated NK ligandsNK cell receptors

Modulation of NK cell activity through the activation of stimulatory receptors or the blockade of inhibitory receptors to enhance anti-tumor immunity (Shimasaki et al., 2020, Nature Reviews Drug Discovery).