Tumor cell surface ligands recognized by Natural Killer (NK) activating and inhibitory receptors (NK cell ligands)

Tumor cell surface ligands recognized by Natural Killer (NK) activating and inhibitory receptors refers to a heterogeneous group of proteins that modulate NK cell activity against malignancies. NK cell function is determined by the integration of signals from a variety of activating receptors (e.g., NKG2D, DNAM-1, NKp30) and inhibitory receptors (e.g., KIRs, NKG2A, TIGIT) [Vivier et al., 2012]. Activating ligands such as MICA, MICB, and ULBPs are often upregulated on tumor cells due to genomic instability or cellular stress, serving as signals for immune recognition [Shimasaki et al., 2020]. Conversely, tumors frequently overexpress inhibitory ligands like HLA-E or PD-L1 to suppress NK cell cytotoxicity and achieve immune evasion [André et al., 2018]. Therapeutic interventions targeting this axis include checkpoint inhibitors that block inhibitory signals (e.g., monalizumab targeting the NKG2A/HLA-E interaction) and NK-cell engagers designed to stabilize the immunological synapse between NK cells and tumor ligands [Demaria et al., 2019]. Understanding the expression profile of these ligands is critical for developing personalized immunotherapy and overcoming resistance mechanisms such as ligand shedding [Schmiedel et al., 2016].

Other names

Natural Killer cell ligandsNK cell receptor ligandsTumor-associated NK ligandsNKLsNK activating and inhibitory ligands

Modulation of the NK cell "rheostat" by either blocking inhibitory ligand-receptor interactions (e.g., HLA-E/NKG2A) or enhancing activating signals (e.g., MICA/NKG2D) to restore anti-tumor cytotoxicity [André et al., 2018; Shimasaki et al., 2020].