Interleukin-2 is required for NKp30-dependent NK cell cytotoxicity by preferentially regulating NKp30 expression

• DOI: 10.3389/fimmu.2024.1388018
• Publication Date: 2024-04-18T04:49:10Z
• Authors: Nayoung Kim; Eunbi Yi; Eunbi Lee; Hyo Jin Park; Hun Sik Kim
• Keywords: Cytotoxicity, Immunologic; 0303 health sciences; Natural Cytotoxicity Triggering Receptor 3; B7 Antigens; Natural Cytotoxicity Triggering Receptor 1; THP-1 Cells; IL-2; Immunology; natural killer cell; acute myeloid leukemia; RC581-607; Killer Cells, Natural; NKp46; 03 medical and health sciences; Humans; Interleukin-2; NKp30; Immunologic diseases. Allergy; K562 Cells

Natural killer (NK) cells are key effectors in cancer immunosurveillance, eliminating a broad spectrum of without major histocompatibility complex (MHC) specificity and graft-versus-host diseases (GvHD) risk. The use allogeneic NK cell therapies from healthy donors has demonstrated favorable clinical efficacies treating diverse cancers, particularly hematologic malignancies, but it requires cytokines such as IL-2 to primarily support persistence expansion. However, the role regulation activating receptors function expanded for trials is poorly understood needs clarification full engagement immunotherapy. Here, we that deprivation significantly impaired cytotoxicity primary by preferentially downregulating NKp30 not NKp46 despite their common adaptor requirement expression function. Using NK92 IL-2-producing NK92MI cells, observed NKp30-mediated against myeloid leukemia K562 THP-1 expressing B7-H6, ligand NKp30, was severely deprivation. Furthermore, deficiency-mediated dysfunction overcome ectopic overexpression an immunostimulatory isoform NKp30a or NKp30b. In particular, improved clearance vivo supplementation. Collectively, our results highlight distinct compared suggest upregulation, shown here overexpression, viable modality harness immunotherapy, possibly combination with immunocytokines.