ArticleCell research2015
Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25.
Article in Cell research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 94 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
94 citing papers in PubMed, 2 syntheses or guidelines pooled it, 157 citations in OpenAlex.
- Biomarkers, measured during therapy, for response of melanoma patients to immune checkpoint inhibitors: a systematic review.Melanoma research · 2019Pooled it
- Immunotherapy as a Promising Treatment for Prostate Cancer: A Systematic Review.Journal of immunology research · 2017Pooled it
- Phase II study of pembrolizumab in refractory esophageal cancer with correlates of response and survival.Journal for immunotherapy of cancer · 2021Trial
- Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Trial
- Immunotherapy: the Mega Weapon to Cure Cancer.Journal of family & reproductive health · 2026Review
- Biomarkers of activity from a phase I study of cergutuzumab amunaleukin in patients with advanced solid tumors.Journal for immunotherapy of cancer · 2026Article
- Synergistic Strategies in Systemic Therapy for Advanced Hepatocellular Carcinoma.Global challenges (Hoboken, NJ) · 2026Review
- Plasma protein dynamics during ipilimumab treatment in metastatic melanoma: associations with tumor response, adverse events and survival.Oncoimmunology · 2025Article
- Improving immunotherapy for the treatment of hepatocellular carcinoma: learning from patients and preclinical models.Gut and liver · 2025Review
- Breast cancer scoring based on a multiplexed profiling of soluble and cell-associated (immune) markers facilitates the prediction of pembrolizumab therapy.Cancer cell international · 2025Article
- Intratumoral Injectable Redox-Responsive Immune Niche Improves the Abscopal Effect in Radiotherapy.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- Optimizing early-phase immunotherapy trials: the role of biomarker enrichment strategies.Frontiers in immunology · 2025Review
- Article
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- Dual Checkpoint Aptamer Immunotherapy: Unveiling Tailored Cancer Treatment Targeting CTLA-4 and NKG2A.Cancers · 2024Article
- Contemporaneous and upcoming trends in immunotherapy for prostate cancer: review.Annals of medicine and surgery (2012) · 2023Article
- PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis.International journal of molecular sciences · 2022Article
- An engineered concealed IL-15-R elicits tumor-specific CD8+T cell responses through PD-1-cis delivery.The Journal of experimental medicine · 2022Article
- Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons.Cell communication and signaling : CCS · 2022Review
- DNA methylation profiles differ in responders versus non-responders to anti-PD-1 immune checkpoint inhibitors in patients with advanced and metastatic head and neck squamous cell carcinoma.Journal for immunotherapy of cancer · 2022Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedErratum: anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25.2015 · Zörnig, Inka [added]; Hassel, Jessica [added]
Authors and funding
33 authors at 13 institutions in 6 countries.
Funding
Abstract
The cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibody ipilimumab induces immune-mediated long-term control of metastatic melanoma in a fraction of patients. Although ipilimumab undoubtedly exerts its therapeutic effects via immunostimulation, thus far clinically useful, immunologically relevant biomarkers that predict treatment efficiency have been elusive. Here, we show that neutralization of IL-2 or blocking the α and β subunits of the IL-2 receptor (CD25 and CD122, respectively) abolished the antitumor effects and the accompanying improvement of the ratio of intratumoral T effector versus regulatory cells (Tregs), which were otherwise induced by CTLA-4 blockade in preclinical mouse models. CTLA-4 blockade led to the reduction of a suppressive CD4(+) T cell subset expressing Lag3, ICOS, IL-10 and Egr2 with a concomitant rise in IL-2-producing effector cells that lost FoxP3 expression and accumulated in regressing tumors. While recombinant IL-2 improved the therapeutic efficacy of CTLA-4 blockade, the decoy IL-2 receptor α (IL-2Rα, sCD25) inhibited the anticancer effects of CTLA-4 blockade. In 262 metastatic melanoma patients receiving ipilimumab, baseline serum concentrations of sCD25 represented an independent indicator of overall survival, with high levels predicting resistance to therapy. Altogether, these results unravel a role for IL-2 and IL-2 receptors in the anticancer activity of CTLA-4 blockade. Importantly, our study provides the first immunologically relevant biomarker, namely elevated serum sCD25, that predicts resistance to CTLA-4 blockade in patients with melanoma.
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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.