ArticleBlood2016
IL-15 activates mTOR and primes stress-activated gene expression leading to prolonged antitumor capacity of NK cells.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
What it found
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Who cites it
106 citing papers in PubMed, 165 citations in OpenAlex.
- Next-generation natural killer cell therapy: bench to bedside and beyond.Signal transduction and targeted therapy · 2026Review
- Siglec-7 orchestrates mitochondrial dynamics and metabolic reprogramming to restrain human NK cell cytotoxic function.The Journal of biological chemistry · 2026Article
- The CREM-IL-15 axis: decoding the persistence-exhaustion paradox in NK cell immunotherapy.Cancer immunology, immunotherapy : CII · 2026Review
- Efficient NK cell transduction with VSV-G-pseudotyped lentiviral vectors.Molecular therapy. Advances · 2026Article
- Activation of M1mAChR's improves spatial learning and memory deficits in rats exposed to chronic intermittent hypoxia.Scientific reports · 2026Article
- Sepsis alters NK cell transcriptional programs for stress, actin remodeling, and intracellular trafficking.Cellular & molecular biology letters · 2026Article
- Anti-IL-15 treatment reduces acute lentivirus inflammation and signaling in the brain.Cell reports. Medicine · 2026Article
- SLy1-deficiency results in functional impaired, exhausted and senescent NK cells.Frontiers in immunology · 2026Article
- Metabolic licensing and restriction of innate immunity in the tumor microenvironment.Frontiers in immunology · 2026Review
- Single-cell analysis of the synovium and infrapatellar fat pad identifies key pathogenic genes and drug targets in osteoarthritis.International journal of clinical and experimental pathology · 2026Article
- Chronic HBV infection impairs the glucose metabolism and effector function of NK cells via HBsAg/IL-15/mTOR axis.Cell death & disease · 2025Article
- Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy.Immune network · 2025Review
- CD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells.Cell reports. Medicine · 2025Article
- Understanding the Mode of Action of Several Active Ingredients from the Micro-Immunotherapy Medicine 2LZONAJournal of inflammation research · 2025Article
- Immunosenescence, Physical Exercise, and their Implications in Tumor Immunity and Immunotherapy.International journal of biological sciences · 2025Review
- Striking a balance: the Goldilocks effect of CD8α expression on NK cells.The Journal of clinical investigation · 2024Article
- A Critical Role of Culture Medium Selection in Maximizing the Purity and Expansion of Natural Killer Cells.Cells · 2024Article
- Induced CD8α identifies human NK cells with enhanced proliferative fitness and modulates NK cell activation.The Journal of clinical investigation · 2024Article
- Natural killer cells drive 4-1BBL positive uveal melanoma towards EMT and metastatic disease.Journal of experimental & clinical cancer research : CR · 2024Article
- Translatomics to explore dynamic differences in immunocytes in the tumor microenvironment.Molecular therapy. Nucleic acids · 2023Review
46 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
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment of hematological malignancies by adoptive transfer of activated natural killer (NK) cells is limited by poor postinfusion persistence. We compared the ability of interleukin-2 (IL-2) and IL-15 to sustain human NK-cell functions following cytokine withdrawal to model postinfusion performance. In contrast to IL-2, IL-15 mediated stronger signaling through the IL-2/15 receptor complex and provided cell function advantages. Genome-wide analysis of cytosolic and polysome-associated messenger RNA (mRNA) revealed not only cytokine-dependent differential mRNA levels and translation during cytokine activation but also that most gene expression differences were primed by IL-15 and only manifested after cytokine withdrawal. IL-15 augmented mammalian target of rapamycin (mTOR) signaling, which correlated with increased expression of genes related to cell metabolism and respiration. Consistently, mTOR inhibition abrogated IL-15-induced cell function advantages. Moreover, mTOR-independent STAT-5 signaling contributed to improved NK-cell function during cytokine activation but not following cytokine withdrawal. The superior performance of IL-15-stimulated NK cells was also observed using a clinically applicable protocol for NK-cell expansion in vitro and in vivo. Finally, expression of IL-15 correlated with cytolytic immune functions in patients with B-cell lymphoma and favorable clinical outcome. These findings highlight the importance of mTOR-regulated metabolic processes for immune cell functions and argue for implementation of IL-15 in adoptive NK-cell cancer therapy.
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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.