ArticleScience translational medicine2015
IL-2Rα mediates temporal regulation of IL-2 signaling and enhances immunotherapy.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
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- Altered Cytokine-Induced STAT3 and STAT5 Activation of Peripheral T Follicular Helper Cells Contributes to Vaccine-Non-Responsiveness in Aging and HIV.Aging cell · 2026Article
- Reshape the Fates of Treg and CD8+T Cells Through IL-2Rα by Synergizing Divergent Receptor-Biased IL-2 PEGylates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Multimodal cell-cell communication driving CD8Frontiers in immunology · 2025Review
- Harnessing CD8 T cell responses using PD-1-IL-2 combination therapy.Trends in cancer · 2024Review
- The combination of IL-2 nanoparticles and Palbociclib enhances the anti-tumor immune response for colon cancer therapy.Frontiers in immunology · 2024Article
- Design and mathematical analysis of activating transcriptional amplifiers that enable modular temporal control in synthetic juxtacrine circuits.Synthetic and systems biotechnology · 2023Article
- IL-2Rα-biased agonist enhances antitumor immunity by invigorating tumor-infiltrating CD25Nature cancer · 2023Article
- Proximity-enabled covalent binding of IL-2 to IL-2Rα selectively activates regulatory T cells and suppresses autoimmunity.Signal transduction and targeted therapy · 2023Article
- PD-1 combination therapy with IL-2 modifies CD8Nature · 2022Article
- Intrinsic IL-2 production by effector CD8 T cells affects IL-2 signaling and promotes fate decisions, stemness, and protection.Science immunology · 2022Article
- B cells imprint adoptively transferred CD8Journal for immunotherapy of cancer · 2022Article
- The ER-Mitochondria Interface as a Dynamic Hub for T Cell Efficacy in Solid Tumors.Frontiers in cell and developmental biology · 2022Review
- Reactive myelopoiesis and the onset of myeloid-mediated immune suppression: Implications for adoptive cell therapy.Cellular immunology · 2021Review
- Heterodimeric IL-15 in Cancer Immunotherapy.Cancers · 2021Review
- Gene-Edited Interleukin CAR-T Cells Therapy in the Treatment of Malignancies: Present and Future.Frontiers in immunology · 2021Review
- CD122-Selective IL2 Complexes Reduce Immunosuppression, Promote Treg Fragility, and Sensitize Tumor Response to PD-L1 Blockade.Cancer research · 2020Article
- Ex vivo blockade of PI3K gamma or delta signaling enhances the antitumor potency of adoptively transferred CD8European journal of immunology · 2020Article
- Adoptive cell therapy of triple negative breast cancer with redirected cytokine-induced killer cells.Oncoimmunology · 2020Article
- Engineered IL-7 Receptor Enhances the Therapeutic Effect of AXL-CAR-T Cells on Triple-Negative Breast Cancer.BioMed research international · 2020Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Interleukin-2 (IL-2) is a lymphocyte growth factor that is an important component of many immune-based cancer therapies. The efficacy of IL-2 is thought to be limited by the expansion of T regulatory cells, which express the high-affinity IL-2 receptor subunit IL-2Rα. IL-15 is under investigation as an alternative to IL-2. Although both cytokines signal through IL-2Rβγ, IL-15 does not bind IL-2Rα and therefore induces less T regulatory cell expansion. However, we found that transferred effector CD8(+) T cells induced curative responses in lymphoreplete mice only with IL-2-based therapy. Although conventional in vitro assays showed similar effector T cell responsiveness to IL-2 and IL-15, upon removal of free cytokine, IL-2 mediated sustained signaling dependent on IL-2Rα. Mechanistically, IL-2Rα sustained signaling by promoting a cell surface IL-2 reservoir and recycling of IL-2 back to the cell surface. Our results demonstrate that IL-2Rα endows T cells with the ability to compete temporally for limited IL-2 via mechanisms beyond ligand affinity. These results suggest that strategies to enhance IL-2Rα expression on tumor-reactive lymphocytes may facilitate the development of more effective IL-2-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 OpenQuestion graph.