Tumor cell surface ligand of NK cell activating receptor

Tumor cell surface ligands for NK cell activating receptors represent a diverse group of molecules induced on stressed, transformed, or infected cells. These ligands are recognized by activating receptors on natural killer (NK) cells—including the NKG2D, DNAM-1, and natural cytotoxicity receptors (NCRs: NKp30, NKp44, NKp46)—which leads to NK cell-mediated cytotoxicity and cytokine release. Such ligands include the MHC class I chain-related proteins (MICA and MICB), UL16 binding proteins (ULBP1–6), PVR (CD155), and Nectin-2, among others[4][5][6]. Surface expression is often absent on normal healthy cells but induced or upregulated during oncogenic transformation or cellular stress, making them a focus of immunotherapeutic strategies. However, tumors can evade immunity by downregulating or shedding these ligands, posing a challenge for therapy[5][6][2].

Other names

NK cell stress-induced ligandNKG2D ligandNCR ligandDNAM-1 ligandSLAM family ligand

Promoting NK cell-mediated cytotoxicity via direct engagement Restoring NK cell activation by blocking inhibitory receptor signaling Antibody-dependent cellular cytotoxicity (ADCC) may be enhanced with some mAbs