ArticleThe Journal of clinical investigation2000
Potential mechanisms of human natural killer cell expansion in vivo during low-dose IL-2 therapy.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Natural Killer Cell-Derived Extracellular Vesicles as a Promising Immunotherapeutic Strategy for Cancer: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Safety and immunologic response of a viral vaccine to prostate-specific antigen in combination with radiation therapy when metronomic-dose interleukin 2 is used as an adjuvant.Clinical cancer research : an official journal of the American Association for Cancer Research · 2008Trial
- Leukemia-targeting NK cell nanoengagers effectively promote robust NK activation and potent anti-acute myeloid leukemia response.Journal of nanobiotechnology · 2026Article
- Chemotherapy driven alterations in NK cell receptors and ligands in high grade serous ovarian cancer.Frontiers in immunology · 2026Article
- Adjusting the scope of natural killer cells in cancer therapy.Cellular & molecular immunology · 2025Review
- Robust differentiation of NK cells from MSLN.CAR-IL-15-engineered human iPSCs with enhanced antitumor efficacy against solid tumors.Science advances · 2025Article
- Clinical, immunologic, and genetic characteristics of 148 patients with natural killer cell deficiency.The Journal of allergy and clinical immunology · 2025Article
- Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy.Immune network · 2025Review
- NKp46 enhances type 1 innate lymphoid cell proliferation and function and anti-acute myeloid leukemia activity.Nature communications · 2025Article
- Imaging-Based Efficacy Evaluation of Cancer Immunotherapy in Engineered Tumor Platforms and Tumor Organoids.Advanced healthcare materials · 2024Review
- Interleukin-2 is required for NKp30-dependent NK cell cytotoxicity by preferentially regulating NKp30 expression.Frontiers in immunology · 2024Article
- The innate defenders: a review of natural killer cell immunotherapies in cancer.Frontiers in immunology · 2024Review
- The prospect of genetically engineering natural killer cells for cancer immunotherapy.Biology open · 2022Review
- CD1d-independent NK1.1Frontiers in immunology · 2022Article
- An Alternative Cell Therapy for Cancers: Induced Pluripotent Stem Cell (iPSC)-Derived Natural Killer Cells.Biomedicines · 2021Review
- CAR-NK Cells in the Treatment of Solid Tumors.International journal of molecular sciences · 2021Review
- A Functional Chemiluminescent Probe for in Vivo Imaging of Natural Killer Cell Activity Against Tumours.Angewandte Chemie (International ed. in English) · 2021Article
- A Functional Chemiluminescent Probe for in Vivo Imaging of Natural Killer Cell Activity Against Tumours.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2021Article
- Cancer immunotherapy with T-cell targeting cytokines: IL-2 and IL-7.BMB reports · 2021Review
- Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The continuous, in vivo infusion of low-dose IL-2 selectively expands the absolute number of human natural killer (NK) cells after 4-6 weeks of therapy. The mechanism responsible for this expansion is unknown and was examined in this study. NK cells cultured at low concentrations of IL-2, comparable to those found during in vivo therapy, proliferate for 6 days and then exit the cell cycle. However, NK cells in vivo did not traverse the S/G(2)/M phase of the cell cycle during low-dose IL-2 therapy. Low concentrations of IL-2 delay programmed cell death of NK cells but have the same effect on resting T cells that do not expand in vivo. When CD34(+) bone marrow hematopoietic progenitor cells are cultured for 21 days with low concentrations of IL-2, they differentiate into CD56(+)CD3(-) NK cells, not T cells. Thus, the selective expansion of human NK cells during continuous in vivo infusion of low-dose IL-2 likely results from enhanced NK-cell differentiation from bone marrow progenitors, combined with an IL-2-dependent delay in NK-cell death, rather than proliferation of mature NK cells in the periphery.
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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.