Tumor cell ligands recognized by NK cell receptors

Tumor cell ligands recognized by NK cell receptors encompass a heterogeneous group of surface proteins that dictate the activation or inhibition of Natural Killer (NK) cells (Vivier et al., 2012, Science). These ligands include stress-induced molecules like MICA, MICB, and ULBPs, which trigger activating receptors such as NKG2D, as well as MHC class I molecules like HLA-E that engage inhibitory receptors like NKG2A (Shimasaki et al., 2020, Nature Reviews Drug Discovery). In many cancers, the balance of these signals is shifted toward inhibition or the loss of activating ligands, allowing tumor cells to evade the innate immune system (Cerwenka and Lanier, 2001, Nature Reviews Immunology). Therapeutic interventions aim to restore NK cell activity by using monoclonal antibodies to block inhibitory checkpoints or by engineering NK cells to better recognize these tumor-associated ligands (Kamiya et al., 2019, Blood). Additionally, some ligands like PVR (CD155) and B7-H6 are being targeted by bispecific engagers to recruit NK cells directly to the tumor site. Consequently, these ligands serve as critical targets for next-generation cancer immunotherapies, including bispecific killer cell engagers (BiKEs) and CAR-NK cell therapies. Understanding the expression patterns of these ligands is essential for patient stratification and monitoring treatment efficacy in oncology.

Other names

NK cell activating ligandsNK cell inhibitory ligandsStress-induced ligandsMHC-related moleculesNK cell receptor ligandsNatural killer cell ligands

Modulation of NK cell activity through the blockade of inhibitory ligand-receptor interactions (e.g., HLA-E/NKG2A) or the engagement of activating ligand-receptor pathways (e.g., MICA/NKG2D) to enhance anti-tumor cytotoxicity.