Natural killer group 2 member D ligand (NKG2D ligand) (NKG2DL)

NKG2D ligands (NKG2DLs) are a family of stress-induced proteins, including MICA, MICB, and the ULBP family, that are upregulated on the surface of cells experiencing genomic instability, malignant transformation, or viral infection [1][2]. These ligands act as critical danger signals that bind to the NKG2D activating receptor (KLRK1) expressed on natural killer (NK) cells and various T-cell subsets, thereby triggering the destruction of the compromised cell [2]. In oncology, NKG2DLs are widely expressed across a broad range of solid and hematological malignancies, making them versatile targets for immunotherapy [4]. However, tumors frequently evade this immune surveillance by proteolytically shedding these ligands from the cell surface, creating soluble decoys that inhibit NKG2D receptor function [2][4]. Current therapeutic strategies targeting NKG2DLs include NKG2D-based chimeric antigen receptor (CAR) T-cells (e.g., CYAD-01), bispecific antibodies, and monoclonal antibodies designed to prevent shedding or enhance immune recognition [3][4]. Sources: [1] UniProt (MICA/MICB); [2] PubMed (PMID: 29463563); [3] Celyad Oncology; [4] Nature Reviews Cancer (PMID: 18695687).

Other names

MICAMICBULBP1ULBP2ULBP3ULBP4ULBP5ULBP6MHC class I polypeptide-related sequence AMHC class I polypeptide-related sequence BStress-induced ligandsTumor cells expressing NKG2D ligands and other stress/activation ligands

Chimeric antigen receptor (CAR) binding to surface ligands; Antibody-dependent cellular cytotoxicity (ADCC); Inhibition of ligand shedding; Bispecific T-cell engagement.