General NK cell-susceptible targets

General NK cell-susceptible targets refers to a functional category of cells, such as the K562 erythroleukemia line, that are inherently vulnerable to Natural Killer (NK) cell-mediated lysis due to their specific molecular profile (PMID: 2211066). These targets typically exhibit a "missing self" phenotype, characterized by the absence or downregulation of Major Histocompatibility Complex (MHC) class I molecules, which normally provide inhibitory signals to NK cells via Killer-cell Immunoglobulin-like Receptors (KIRs) (PMID: 11491521). Additionally, they often express "induced self" ligands, such as MICA, MICB, and UL16-binding proteins (ULBPs), which trigger activating receptors like NKG2D (PMID: 21734677). In therapeutic development, this concept is utilized to design drugs that sensitize tumor cells to NK cells or activate NK cells directly, including checkpoint inhibitors like Monalizumab and bispecific engagers like AFM13 (PMID: 30503213, 33097614). The susceptibility of these targets is a critical parameter in evaluating the efficacy of adoptive cell therapies and immunomodulatory agents in cancer and viral infections.

Other names

NK cell ligandsNK-sensitive targetsNK cell-susceptible cellsActivating NK cell ligandsStress-induced ligands

Enhancement of NK cell-mediated cytotoxicity through the engagement of activating receptors or blockade of inhibitory checkpoints.