NK cell receptor ligands on tumor cells

NK cell receptor ligands on tumor cells are a heterogeneous group of proteins upregulated or expressed anew in response to cellular stress, malignant transformation, or infection. Key families include the MHC class I chain-related proteins (MICA, MICB), UL16-binding proteins (ULBP1-6), nectin/nectin-like molecules (CD155, CD112), and B7 family members (such as B7-H6). Their expression on tumor cells enables recognition and direct cytotoxicity by NK cells via activating receptors like NKG2D, NKp30, and NKp44. Simultaneously, some ligands interact with inhibitory NK cell receptors (e.g., HLA-E binding to NKG2A, HLA-G to certain KIRs), allowing tumors to evade immune destruction. The dynamic regulation and shedding of these ligands contribute to immune escape and are directly implicated in cancer progression. Accordingly, modulation of these ligand-receptor interactions represents a promising but complex therapeutic strategy in oncology.

Other names

Activating NK cell receptor ligandsNKG2D ligandsNCR ligandsstress-induced ligandstumor cell ligands

Blockade of inhibitory NK cell receptor signaling, restoring NK cytotoxicity; Enhancement of activating signaling by upregulation/presentation of activating ligands; Interference with ligand-receptor interactions to prevent tumor immune evasion; Immune checkpoint blockade to augment antitumor response