ArticleFrontiers in immunology2024
Interleukin-2 is required for NKp30-dependent NK cell cytotoxicity by preferentially regulating NKp30 expression.
Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Ascites reprograms innate lymphoid immune cells in ovarian cancer by promoting ILC2 enrichment and dysfunctional NK-cell states.Journal for immunotherapy of cancer · 2026Article
- Kindlin-3 sustains cytokine interleukin-2 signaling by linking its receptor to integrin LFA-1.The Journal of biological chemistry · 2026Article
- Efficient, fratricide free non-viral engineering of CD70-targeted CAR NK cells for hematologic and solid tumor immunotherapy.Molecular therapy. Advances · 2026Article
- Targeting NK cell CLEC12B enhances cancer immunotherapy.Nature immunology · 2026Article
- Peripheral cytokines as candidate biomarkers for recurrent pregnancy loss.Reproduction & fertility · 2026Article
- A new era in CAR-NK cell therapy: from technological innovations to clinical applications.World journal of pediatrics : WJP · 2026Review
- Interaction of CD99 and its ligands regulates immunoregulatory pathways in NK cells.Frontiers in immunology · 2026Article
- Sensory Characteristics of Probiotic-Containing Foods: A Multidisciplinary Perspective on Enhancing Acceptability and Consumer Adherence.Nutrients · 2025Review
- Anti-FAP CAR-NK cells as a novel targeted therapy against cervical cancer and cancer-associated fibroblasts.Oncoimmunology · 2025Article
- Targeting SHP-1-Mediated Inhibition of STAT3 and ERK Signalling Pathways Rescues the Hyporesponsiveness of MHC-I-Deficient NK-92MI.Cell proliferation · 2025Article
- NKp30: A Key Membrane Molecule in the Fight Against Cancer and Infection.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Adjusting the scope of natural killer cells in cancer therapy.Cellular & molecular immunology · 2025Review
- Lymphocytes and monocytes undergo swift suppression of IL-10R, IL-6R, and IL-2Rβγ signaling under high concentrations of different cytokines.bioRxiv : the preprint server for biology · 2025Article
- Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy.Immune network · 2025Review
- A New Antibody-Cytokine Construct Targeting Natural Killer Cells: An Immunotherapeutic Approach to Chronic Lymphocytic Leukemia.Biomolecules · 2025Article
- Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments.International journal of molecular sciences · 2024Review
- Natural killer cell engagers for cancer immunotherapy.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cells are key effectors in cancer immunosurveillance, eliminating a broad spectrum of cancer cells without major histocompatibility complex (MHC) specificity and graft-versus-host diseases (GvHD) risk. The use of allogeneic NK cell therapies from healthy donors has demonstrated favorable clinical efficacies in treating diverse cancers, particularly hematologic malignancies, but it requires cytokines such as IL-2 to primarily support NK cell persistence and expansion. However, the role of IL-2 in the regulation of activating receptors and the function of NK cells expanded for clinical trials is poorly understood and needs clarification for the full engagement of NK cells in cancer immunotherapy. Here, we demonstrated that IL-2 deprivation significantly impaired the cytotoxicity of primary expanded NK cells by preferentially downregulating NKp30 but not NKp46 despite their common adaptor requirement for expression and function. Using NK92 and IL-2-producing NK92MI cells, we observed that NKp30-mediated cytotoxicity against myeloid leukemia cells such as K562 and THP-1 cells expressing B7-H6, a ligand for NKp30, was severely impaired by IL-2 deprivation. Furthermore, IL-2 deficiency-mediated NK cell dysfunction was overcome by the ectopic overexpression of an immunostimulatory NKp30 isoform such as NKp30a or NKp30b. In particular, NKp30a overexpression in NK92 cells improved the clearance of THP-1 cells
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