ArticleThe Journal of experimental medicine2022
Differential IL-12 signaling induces human natural killer cell activating receptor-mediated ligand-specific expansion.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Immunological Activity of Vaccine Systems Containing Liposomal Nanocarriers against Protozoan-induced Diseases: A Systematic Review.Current medicinal chemistry · 2025Pooled it
- Effects of rice bran arabinoxylan compound on quality of life of cancer patients during active treatment: a randomised placebo-controlled pilot trial.Scientific reports · 2026Trial
- 25 Years of Cancer Immunoediting: Dendritic Cells and Macrophages Filled the Missing Gap.Cancers · 2026Review
- Safety and Feasibility of Infusing Ex Vivo Expanded Allogeneic Canine Natural Killer Cells for the Treatment of Metastatic Solid Tumours.Veterinary and comparative oncology · 2026Article
- Safety and Feasibility of InfusingbioRxiv : the preprint server for biology · 2026Article
- Targeting IL-12 for pancreatic cancer immunotherapy: advances in delivery strategies and clinical translation.Frontiers in immunology · 2026Review
- Phantom of the immunologic opera: Unmasking the role of innate lymphoid cells (ILC) in inborn errors of immunity (IEI).Journal of human immunity · 2025Review
- Article
- Adjusting the scope of natural killer cells in cancer therapy.Cellular & molecular immunology · 2025Review
- The Role and Potential Application of IL-12 in the Immune Regulation of Tuberculosis.International journal of molecular sciences · 2025Review
- Short-term oral zinc supplementation enhances Natural Killer cell functionality and decreases circulating Innate Lymphoid Cell counts and frequencies in healthy young adults.Journal of translational medicine · 2025Article
- EpCAM Signaling in Oral Cancer Stem Cells: Implications for Metastasis, Tumorigenicity, and Therapeutic Strategies.Current issues in molecular biology · 2025Review
- CITE-Seq Analysis Reveals a Differential Natural Killer CellInternational journal of molecular sciences · 2025Article
- Oncolytic cytomegaloviruses expressing EGFR-retargeted fusogenic glycoprotein complex and drug-controllable interleukin 12.Cell reports. Medicine · 2025Article
- Inflammatory, Functional, and Compositional Changes of the Uterine Immune Microenvironment in a Lymphangioleiomyomatosis Mouse Model.Journal of cellular immunology · 2025Article
- Understanding the Mode of Action of Several Active Ingredients from the Micro-Immunotherapy Medicine 2LZONAJournal of inflammation research · 2025Article
- Antiproliferative and pro-apoptotic effects ofFrontiers in oncology · 2025Article
- Natural killer cell memory: challenges and opportunities for cancer immunotherapy.Cancer biology & therapy · 2024Review
- CD2 expressing innate lymphoid and T cells are critical effectors of immunopathogenesis in hidradenitis suppurativa.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions.Signal transduction and targeted therapy · 2024Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
IL-12 is an essential cytokine involved in the generation of memory or memory-like NK cells. Mouse cytomegalovirus infection triggers NK receptor-induced, ligand-specific IL-12-dependent NK cell expansion, yet specific IL-12 stimulation ex vivo leading to NK cell proliferation and expansion is not established. Here, we show that IL-12 alone can sustain human primary NK cell survival without providing IL-2 or IL-15 but was insufficient to promote human NK cell proliferation. IL-12 signaling analysis revealed STAT5 phosphorylation and weak mTOR activation, which was enhanced by activating NK receptor upregulation and crosslinking leading to STAT5-dependent, rapamycin-sensitive, or TGFβ-sensitive NK cell IL-12-dependent expansion, independently of IL-12 receptor upregulation. Prolonged IL-2 culture did not impair IL-12-dependent ligand-specific NK cell expansion. These findings demonstrate that activating NK receptor stimulation promotes differential IL-12 signaling, leading to human NK cell expansion, and suggest adopting strategies to provide IL-12 signaling in vivo for ligand-specific IL-2-primed NK cell-based therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.