ArticleThe Journal of experimental medicine2013
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 896 papers, 2 of them syntheses 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.
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Who cites it
896 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,432 citations in OpenAlex.
- Immune checkpoint inhibitors-associated cranial nerves involvement: a systematic literature review on 136 patients.Journal of neurology · 2024Pooled it
- Efficacy and safety of nivolumab plus ipilimumab in gastrointestinal cancers: a systematic review and meta-analysis.Frontiers in oncology · 2024Pooled it
- Trial
- Neoadjuvant Fc-enhanced anti-CTLA-4 targets Tregs to augment androgen deprivation in high-risk prostate cancer: A randomized phase I trial.Cell reports. Medicine · 2026Trial
- Depletion of Effector Regulatory T Cells Associates with Major Response to Induction Dual Immune Checkpoint Blockade.Cancer discovery · 2025Trial
- Dual Immune Checkpoint Inhibition Plus Neoadjuvant Chemoradiotherapy in Rectal Cancer: A Randomized Clinical Trial.JAMA network open · 2025Trial
- Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple-negative breast cancer: a phase 2 adaptive trial.Nature medicine · 2024Trial
- Ipilimumab and nivolumab combined with anthracycline-based chemotherapy in metastatic hormone receptor-positive breast cancer: a randomized phase 2b trial.Journal for immunotherapy of cancer · 2024Trial
- Inhibitory receptor profiles for joint prediction of benefit and toxicity in immune checkpoint blockade.iScience · 2026Review
- Quantitative Systems Pharmacology Model Predicts Enhanced Antitumor Efficacy of Combined Cytotoxic T‑Lymphocyte-Associated Protein 4 (CTLA-4) and Programmed Cell Death Protein 1 (PD-1) Blockade in a Syngeneic Mouse Model of Breast Cancer.ACS pharmacology & translational science · 2026Article
- Why antibody isotype matters for immunotherapy.Antibody therapeutics · 2026Review
- Targeting the Tumor Microenvironment Network to Overcome Immunotherapy Resistance in Non-Small Cell Lung Cancer: Mechanisms to Clinical Translation.Cancer medicine · 2026Review
- Review
- Immune-pressure redistribution in resistance to PD-1/PD-L1 blockade: mechanisms, biomarkers, and therapeutic design.Molecular cancer · 2026Review
- Review
- Spatially-resolved single-cell imaging of melanoma brain metastases identifies localized immune patterns predictive of immune checkpoint blockade response.Neuro-oncology · 2026Article
- Fc-optimized GITR antibody enhances a CD4 T cell-dendritic cell crosstalk to promote antitumor immunity.Nature cancer · 2026Article
- Fc-engineering for improved cancer immunotherapy.Biochemical Society transactions · 2026Review
- Article
- Intratumoral Regulatory T-cell Ablation Mediates Tumor Control Systemically without Autoimmunity.Cancer research · 2026Article
836 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
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Treatment with monoclonal antibody specific for cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), an inhibitory receptor expressed by T lymphocytes, has emerged as an effective therapy for the treatment of metastatic melanoma. Although subject to debate, current models favor a mechanism of activity involving blockade of the inhibitory activity of CTLA-4 on both effector (T eff) and regulatory (T reg) T cells, resulting in enhanced antitumor effector T cell activity capable of inducing tumor regression. We demonstrate, however, that the activity of anti-CTLA-4 antibody on the T reg cell compartment is mediated via selective depletion of T reg cells within tumor lesions. Importantly, T reg cell depletion is dependent on the presence of Fcγ receptor-expressing macrophages within the tumor microenvironment, indicating that T reg cells are depleted in trans in a context-dependent manner. Our results reveal further mechanistic insight into the activity of anti-CTLA-4-based cancer immunotherapy, and illustrate the importance of specific features of the local tumor environment on the final outcome of antibody-based immunomodulatory 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.