Tumor cell surface ligands recognized by METR-NK cells

Tumor cell surface ligands recognized by METR-NK cells refer to a collective group of stress-induced and tumor-associated proteins that serve as the primary targets for metabolically remodeled natural killer (METR-NK) cells. These ligands primarily include the NKG2D ligand family, such as MHC class I polypeptide-related sequences A and B (MICA/B) and UL16-binding proteins (ULBP1-6), as well as ligands for natural cytotoxicity receptors (NCRs) like B7-H6 (1.1.1, 1.4.4). METR-NK cells are a specialized therapeutic product, such as those developed by Anhui Kecheng Intelligent Health Technology, which undergo metabolic reprogramming during ex vivo expansion to enhance their cytotoxicity, delay senescence, and improve their functional resilience within the immunosuppressive tumor microenvironment (1.2.3, 1.3.1). In a clinical context, these ligands are highly expressed on various solid tumors, including advanced epithelial ovarian cancer, while remaining largely absent from healthy tissues, providing a window for targeted immunotherapy (1.1.1, 1.2.4). When METR-NK cells encounter these ligands, their activating receptors (such as NKG2D and NKp30) transmit potent signals that override inhibitory cues, resulting in the directed release of cytolytic molecules and the induction of tumor cell apoptosis (1.1.1, 1.4.5). Current research and clinical trials, such as NCT06395844, are evaluating the safety and efficacy of intraperitoneally administered METR-NK cells as neoadjuvant therapy for ovarian cancer, focusing on their ability to recognize these surface markers and eliminate metastatic lesions (1.2.1, 1.2.3).

Other names

NK cell activating ligandsStress-induced ligandsNKG2D ligandsNatural cytotoxicity receptor ligandsNCR ligandsMICA/B and ULBPs

METR-NK cells (Metabolic Remodeling Natural Killer cells) are engineered to recognize and bind to specific activating ligands on the surface of tumor cells, such as MICA/B and ULBPs, via their native or enhanced activating receptors (e.g., NKG2D, NKp30, NKp44). This binding triggers the release of cytotoxic granules containing perforin and granzymes, leading to direct tumor cell lysis and the secretion of pro-inflammatory cytokines like IFN-gamma to further stimulate the anti-tumor immune response (1.1.1, 1.2.3).