ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Durable therapeutic efficacy utilizing combinatorial blockade against IDO, CTLA-4, and PD-L1 in mice with brain tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. 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 373 papers, 5 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
373 citing papers in PubMed, 5 syntheses or guidelines pooled it, 576 citations in OpenAlex.
- Comparative efficacy of glioma treatment strategies: an umbrella review of meta-analyses.Annals of medicine · 2025Pooled it
- A systematic review of immunotherapy in high-grade glioma: learning from the past to shape future perspectives.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Pooled it
- Research hotspots and trend of glioblastoma immunotherapy: a bibliometric and visual analysis.Frontiers in oncology · 2024Pooled it
- The efficacy and safety of anti-PD-1/PD-L1 in treatment of glioma: a single-arm meta-analysis.Frontiers in immunology · 2023Pooled it
- PD-L1 Expression in Glioblastoma, the Clinical and Prognostic Significance: A Systematic Literature Review and Meta-Analysis.Frontiers in oncology · 2020Pooled it
- Neoadjuvant PD1 plus CTLA-4 immune checkpoint blockade in surgically resectable recurrent glioblastoma: a randomized surgical window-of-opportunity trial.Nature communications · 2026Trial
- Radiomics-Based Machine Learning for Outcome Prediction in a Multicenter Phase II Study of Programmed Death-Ligand 1 Inhibition Immunotherapy for Glioblastoma.AJNR. American journal of neuroradiology · 2022Trial
- Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma.Journal for immunotherapy of cancer · 2021Trial
- Differentiation therapy targeting indoleamine 2,3-dioxygenase 1 in glioblastoma cellsMolecular and clinical oncology · 2026Article
- Phase I Evaluation of Patients with Newly Diagnosed Glioblastoma Treated with Radiation, Nivolumab, and IDO1 Enzyme Inhibitor BMS-986205.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Targeting tryptophan metabolism in breast cancer immunotherapy: Recent advances and future prospects.Translational oncology · 2026Review
- IL6 Supports Development of an Immunosuppressive Microenvironment and Resistance to Therapy in Glioblastoma.Cancer research · 2026Article
- Decoding glioblastoma evolution and heterogeneity through mechanistic modeling: implications for clinical translation.Journal of experimental & clinical cancer research : CR · 2026Review
- Dynamic remodeling of amino acid metabolism in tumor-associated macrophages: Fueling immunosuppression, reshaping tumor niches, and unlocking metabolic checkpoints.Journal of advanced research · 2026Review
- The promise of immunotherapy for central nervous system tumours.Nature reviews. Immunology · 2026Review
- Metabolic cell competition in the glioblastoma tumour microenvironment: glucose, glutamine, and lactate as determinants of immune exclusion and targets for pharmacological reprogramming.Frontiers in oncology · 2026Review
- Microenvironment-defined priority pathways shape ICD-driven abscopal responses.Frontiers in immunology · 2026Review
- Next-Generation Immune Checkpoints and Tumor Microenvironment Modulation in Cancer Immunotherapy.Journal of immunology research · 2026Review
- Targeting Tumor-Infiltrating Immune Cells for Targeted Alpha Therapy in Gliomas: Optimization of [225Ac]Ac-DOTA-αCD11b Dosing through PET Imaging.Molecular cancer therapeutics · 2025Article
- Newly diagnosed glioblastoma IDHwt patients treated with radiation, nivolumab, and BMS-986205.Research square · 2025Article
313 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
purposeGlioblastoma (GBM) is the most common form of malignant glioma in adults. Although protected by both the blood-brain and blood-tumor barriers, GBMs are actively infiltrated by T cells. Previous work has shown that IDO, CTLA-4, and PD-L1 are dominant molecular participants in the suppression of GBM immunity. This includes IDO-mediated regulatory T-cell (Treg; CD4(+)CD25(+)FoxP3(+)) accumulation, the interaction of T-cell-expressed, CTLA-4, with dendritic cell-expressed, CD80, as well as the interaction of tumor- and/or macrophage-expressed, PD-L1, with T-cell-expressed, PD-1. The individual inhibition of each pathway has been shown to increase survival in the context of experimental GBM. However, the impact of simultaneously targeting all three pathways in brain tumors has been left unanswered. EXPERIMENTAL DESIGN AND
resultsIn this report, we demonstrate that, when dually challenged, IDO-deficient tumors provide a selectively competitive survival advantage against IDO-competent tumors. Next, we provide novel observations regarding tryptophan catabolic enzyme expression, before showing that the therapeutic inhibition of IDO, CTLA-4, and PD-L1 in a mouse model of well-established glioma maximally decreases tumor-infiltrating Tregs, coincident with a significant increase in T-cell-mediated long-term survival. In fact, 100% of mice bearing intracranial tumors were long-term survivors following triple combination therapy. The expression and/or frequency of T cell expressed CD44, CTLA-4, PD-1, and IFN-γ depended on timing after immunotherapeutic administration.
conclusionsCollectively, these data provide strong preclinical evidence that combinatorially targeting immunosuppression in malignant glioma is a strategy that has high potential value for future clinical trials in patients with GBM.
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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.