Tumor cell surface antigen recognized by natural killer cell activating receptor

Tumor cell surface antigens recognized by activating receptors on natural killer cells are a diverse set of stress-induced proteins or glycoproteins expressed on tumor cells in response to malignant transformation, cellular stress, or infection. These antigens include the ligands for major NK cell activating receptors such as NKG2D (e.g., MICA, MICB, ULBP1-6) and the natural cytotoxicity receptors (NCRs: NKp30, NKp44, NKp46), whose ligands (e.g., B7-H6 for NKp30, externalized calreticulin for NKp46) are minimally present on healthy cells but upregulated on diseased cells. Engagement of these ligands by their cognate NK cell receptors leads to NK cell activation, cytotoxicity, and secretion of cytokines, thereby contributing to tumor immunosurveillance and the therapeutic mechanism of action for antibody therapies that utilize NK cell-mediated killing[1][2][3][4][5][6]. Note: For structured databases, this entry needs to be resolved to specific antigens (such as “MHC class I polypeptide-related sequence A [MICA],” “UL16-binding protein 1 [ULBP1],” “B7 homolog 6 [B7-H6],” etc.), corresponding to the specific NK cell activating receptor of interest. The current query groups many targets under a single, non-standard descriptor.

Other names

Ligand for NK cell activating receptorStress-induced ligand (on tumor cells)Ligand for NKG2D, NKp30, NKp44, NKp46

Antibody-dependent cellular cytotoxicity (ADCC) via NK cell Fc receptor (CD16) recognizing therapeutic antibody Fc region; Enhancement of NK cell-mediated cytotoxicity by upregulation of activating ligands (e.g., via DNA-damaging agents or other therapies)