Nkp46, also known as NCR1 or CD335, a key activating receptor of the immunoglobulin superfamily with dual C2-type extracellular domains, is essential for innate cytotoxicity and cytokine production in NK cells and type 1 innate lymphoid cells (ILC1s). It triggers cell activation by associating with ITAM-bearing adaptors CD3ζ/FcεRγ, initiating signaling cascades that enhance cytotoxic granule release and interferon-γ production. Studies highlight its critical role in controlling acute myeloid leukemia through NF-κB-mediated IL-2Rα upregulation in liver-resident ILC1s, enabling proliferative expansion and tumoricidal activity. Nkp46 also mediates viral defense by recognizing hemagglutinins on influenza-infected cells. These mechanisms underpin its therapeutic potential in cancer immunotherapy, particularly for developing antibody-based strategies to amplify NK/ILC1 antitumor responses.
Fig.1 Molecular structures of Nkp46.1
Reference
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