Natural killer cell inhibitory receptor (NKIR)

Natural killer (NK) cell inhibitory receptors are a diverse group of cell surface proteins that play a critical role in regulating the immune system's ability to distinguish between healthy self-cells and abnormal cells, such as those infected by viruses or transformed into cancer (Vivier et al., 2011, Science) [1]. These receptors, which include the killer cell immunoglobulin-like receptors (KIRs) and the C-type lectin-like receptor NKG2A, primarily recognize major histocompatibility complex (MHC) class I molecules on the surface of target cells (Long et al., 2013, Annu Rev Immunol) [2]. When these receptors bind to their ligands, they transmit inhibitory signals via immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that prevent NK cell activation and the subsequent release of cytotoxic granules (Long et al., 2013, Annu Rev Immunol) [2]. This mechanism is essential for maintaining self-tolerance and preventing the destruction of healthy tissues. However, many tumors exploit this system by overexpressing inhibitory ligands, such as HLA-E, to evade immune detection and suppress NK cell-mediated surveillance (André et al., 2018, Cell) [3]. Therapeutic interventions, such as monoclonal antibodies like monalizumab and lirilumab, are designed to block these inhibitory interactions, thereby restoring the NK cells' natural capacity to kill malignant cells (NCI Drug Dictionary) [4]. These checkpoint inhibitors for NK cells are currently being evaluated in clinical trials for their potential to treat various cancers, often in combination with other immunotherapies to enhance overall anti-tumor efficacy (André et al., 2018, Cell) [3].

Other names

Killer cell immunoglobulin-like receptorKIRNKG2ACD159aLILRB1ILT2Immune checkpoint receptor

Inhibitory checkpoint blockade to enhance NK cell-mediated anti-tumor activity