ArticleThe Journal of clinical investigation2014
IL-2 therapy promotes suppressive ICOS+ Treg expansion in melanoma patients.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 1 of them a synthesis that pooled it.
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
146 citing papers in PubMed, 1 synthesis or guideline pooled it, 224 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- Nemvaleukin alfa monotherapy in patients with advanced melanoma and renal cell carcinoma: results from the phase 1/2 non-randomized ARTISTRY-1 trial.Journal for immunotherapy of cancer · 2025Trial
- Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1).Journal for immunotherapy of cancer · 2024Trial
- Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study.Nature communications · 2024Trial
- TransCon IL-2 β/γ: a novel long-acting prodrug with sustained release of an IL-2Rβ/γ-selective IL-2 variant with improved pharmacokinetics and potent activation of cytotoxic immune cells for the treatment of cancer.Journal for immunotherapy of cancer · 2022Trial
- Immune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma.Nature communications · 2021Trial
- Bempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy.Nature communications · 2020Trial
- Radiotherapy induces responses of lung cancer to CTLA-4 blockade.Nature medicine · 2018Trial
- Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial.PLoS medicine · 2016Trial
- Engineered probioticScience advances · 2026Article
- Advances in Cancer Immunotherapy for Solid Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Inducible T-Cell Co-Stimulator (ICOS) and ICOS Ligand: Dealing With a Two-Faced Cancer Immunoregulatory System.Cancer medicine · 2026Review
- Article
- The application and prospect of granzyme B-targeted PET imaging in cancer immunotherapy.Journal of translational medicine · 2025Review
- Current landscape and future prospects of interleukin-2 receptor (IL-2R) agonists in cancer immunotherapy.Oncoimmunology · 2025Review
- Dual targeting OX40 and IL-2 receptor enhances antitumor activity through tumor-infiltrating Treg depletion and CD8Journal for immunotherapy of cancer · 2025Article
- Regulatory T cells in the tumour microenvironment.Nature reviews. Cancer · 2025Review
- Regulatory T cells in liver metastases: emerging and divergent roles in tumour progression.eGastroenterology · 2025Review
- ICOS and ICOS ligand: expression patterns and outcomes in oncology patients.Therapeutic advances in medical oncology · 2025Article
- Impact of T cell characteristics on CAR-T cell therapy in hematological malignancies.Blood cancer journal · 2024Review
86 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 2 institutions in 2 countries.
Funding
Abstract
High-dose (HD) IL-2 therapy in patients with cancer increases the general population of Tregs, which are positive for CD4, CD25, and the Treg-specific marker Foxp3. It is unknown whether specific subsets of Tregs are activated and expanded during HD IL-2 therapy or whether activation of any particular Treg subset correlates with clinical outcome. Here, we evaluated Treg population subsets that were induced in patients with melanoma following HD IL-2 therapy. We identified a Treg population that was positive for CD4, CD25, Foxp3, and the inducible T cell costimulator (ICOS). This Treg population increased more than any other lymphocyte subset during HD IL-2 therapy and had an activated Treg phenotype, as indicated by high levels of CD39, CD73, and TGF-β. ICOS(+) Tregs were the most proliferative lymphocyte population in the blood after IL-2 therapy. Patients with melanoma with enhanced expansion of ICOS(+) Tregs in blood following the first cycle of HD IL-2 therapy had worse clinical outcomes than patients with fewer ICOS(+) Tregs. However, there was no difference in total Treg expansion between HD IL-2 responders and nonresponders. These data suggest that increased expansion of the ICOS(+) Treg population following the first cycle of HD IL-2 therapy may be predictive of clinical outcome.
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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.