ArticleJournal of immunology (Baltimore, Md. : 1950)2015
IL-15 Superagonist-Mediated Immunotoxicity: Role of NK Cells and IFN-γ.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 99 citations in OpenAlex.
- Meditope-Enabled Chimeric Antigen Receptors Facilitate Plug-and-Play Control of T Cells.Cancer immunology research · 2026Article
- αTIGIT-guided IL-15 mimetics drive potent and safe antitumor immunity by restoring tumor-infiltrating T cells.Cellular & molecular immunology · 2026Article
- NF-κB-driven immune checkpoint knockdown and cytokine expression in cancer cells for tumor immunotherapy.iScience · 2026Article
- Multifunctional-engineered NK cells overcome tumor immunosuppression by combining PD-L1 and HLA-E targeting and endogenous IL15 production.Signal transduction and targeted therapy · 2026Article
- PD-1-targeted IL-15 mutein activates CD8+ and CD4+ T cells in infection and cancer.JCI insight · 2026Article
- Retinoids enhance NK effector function against HIV-infected CD4 T cells.Journal of virology · 2026Article
- Quantitative assessment of extravasation of IL-15-secreting MSLN-CAR-NK-92 cells using tumor transparency imaging.Theranostics · 2026Article
- Type I interferon regulation of group I ILC subsets during both homeostasis and cytomegalovirus infection.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Probiotic-mediated tumor microenvironment reprogramming with protease-sensitive interleukin-15 and photothermal therapy.Cell reports. Medicine · 2025Article
- Concurrent intratumoural TNature biomedical engineering · 2025Article
- Advances of oncolytic vaccinia viruses armed with interleukin in tumor therapy.Frontiers in oncology · 2025Review
- A tumor-conditional IL-15 safely synergizes with immunotherapy to enhance antitumor immune responses.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Nanoenabled IL-15 Superagonist via Conditionally Stabilized Protein-Protein Interactions Eradicates Solid Tumors by Precise Immunomodulation.Journal of the American Chemical Society · 2024Article
- IL2 Targeted to CD8+ T Cells Promotes Robust Effector T-cell Responses and Potent Antitumor Immunity.Cancer discovery · 2024Article
- Preclinical Evaluation of Off-The-Shelf PD-L1+ Human Natural Killer Cells Secreting IL15 to Treat Non-Small Cell Lung Cancer.Cancer immunology research · 2024Article
- Effect of ethanol exposure on innate immune response in sepsis.Journal of leukocyte biology · 2024Review
- Pharmacokinetics, pharmacodynamics, and toxicity of a PD-1-targeted IL-15 in cynomolgus monkeys.PloS one · 2024Article
- Immunoadjuvant therapy in the regulation of cell death in sepsis: recent advances and future directions.Frontiers in immunology · 2024Review
- Therapeutic approaches to enhance natural killer cell cytotoxicity.Frontiers in immunology · 2024Review
- CD8+ Regulatory T Cells Induced by Lipopolysaccharide Improve Mouse Endotoxin Shock.ImmunoHorizons · 2023Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
IL-15 is currently undergoing clinical trials to assess its efficacy for treatment of advanced cancers. The combination of IL-15 with soluble IL-15Rα generates a complex termed IL-15 superagonist (IL-15 SA) that possesses greater biological activity than IL-15 alone. IL-15 SA is considered an attractive antitumor and antiviral agent because of its ability to selectively expand NK and memory CD8(+) T (mCD8(+) T) lymphocytes. However, the adverse consequences of IL-15 SA treatment have not been defined. In this study, the effect of IL-15 SA on physiologic and immunologic functions of mice was evaluated. IL-15 SA caused dose- and time-dependent hypothermia, weight loss, liver injury, and mortality. NK (especially the proinflammatory NK subset), NKT, and mCD8(+) T cells were preferentially expanded in spleen and liver upon IL-15 SA treatment. IL-15 SA caused NK cell activation as indicated by increased CD69 expression and IFN-γ, perforin, and granzyme B production, whereas NKT and mCD8(+) T cells showed minimal, if any, activation. Cell depletion and adoptive transfer studies showed that the systemic toxicity of IL-15 SA was mediated by hyperproliferation of activated NK cells. Production of the proinflammatory cytokine IFN-γ, but not TNF-α or perforin, was essential to IL-15 SA-induced immunotoxicity. The toxicity and immunological alterations shown in this study are comparable to those reported in recent clinical trials of IL-15 in patients with refractory cancers and advance current knowledge by providing mechanistic insights into IL-15 SA-mediated immunotoxicity.
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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 OpenQuestion graph.