ArticleNeuro-oncology2009
Regulatory T cells and the PD-L1/PD-1 pathway mediate immune suppression in malignant human brain tumors.
Article in Neuro-oncology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 3 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
147 citing papers in PubMed, 3 syntheses or guidelines pooled it, 254 citations in OpenAlex.
- T cell immunity in glioma and potential implications for immunotherapy: A systematic review.Neuro-oncology · 2026Pooled it
- Blood-Based Biomarkers for Glioma in the Context of Gliomagenesis: A Systematic Review.Frontiers in oncology · 2021Pooled it
- Comparative effect of immunotherapy and standard therapy in patients with high grade glioma: a meta-analysis of published clinical trials.Scientific reports · 2018Pooled it
- Review
- Review
- Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Metal-based nanomaterials achieve tumor treatment strategies by overcoming the blood-brain barrier of glioma and responding to the tumor microenvironment.Materials today. Bio · 2026Review
- 5-ALA Assisted Surgery of Human Glioblastoma Samples Reveals an Enrichment of T Cells Expressing PD-1 and CD103 in the Intermediate and Marginal Layers.European journal of immunology · 2025Article
- Tumor Microenvironment in Melanoma Brain Metastasis: A New Potential Target?International journal of molecular sciences · 2025Review
- The Role of Tregs in the Tumor Microenvironment.Biomedicines · 2025Review
- A Nexus of Biomolecular Complexities in Pituitary Neuroendocrine Tumors: Insights into Key Molecular Drivers.Biomedicines · 2025Review
- The Role of Gut Microbiome on Glioblastoma Oncogenesis and Malignant Evolution.International journal of molecular sciences · 2025Review
- Article
- Article
- The immune landscape in brain metastasis.Neuro-oncology · 2025Review
- Tumor cell-derived spermidine promotes a protumorigenic immune microenvironment in glioblastoma via CD8+ T cell inhibition.The Journal of clinical investigation · 2024Article
- Pathomics models for CD40LG expression and prognosis prediction in glioblastoma.Scientific reports · 2024Article
- Spatial cell interplay networks of regulatory T cells predict recurrence in patients with operable non-small cell lung cancer.Cancer immunology, immunotherapy : CII · 2024Article
- Defining Human Regulatory T Cells beyond FOXP3: The Need to Combine Phenotype with Function.Cells · 2024Review
- The biological behavior and clinical outcome of pituitary adenoma are affected by the microenvironment.CNS neuroscience & therapeutics · 2024Review
87 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
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The brain is a specialized immune site representing a unique tumor microenvironment. The availability of fresh brain tumor material for ex vivo analysis is often limited because large parts of many brain tumors are resected using ultrasonic aspiration. We analyzed ultrasonic tumor aspirates as a biosource to study immune suppressive mechanisms in 83 human brain tumors. Lymphocyte infiltrates in brain tumor tissues and ultrasonic aspirates were comparable with respect to lymphocyte content and viability. Applying ultrasonic aspirates, we detected massive infiltration of CD4+FoxP3+CD25(high) CD127(low) regulatory T cells (Tregs) in glioblastomas (n = 29) and metastatic brain tumors (n = 20). No Treg accumulation was observed in benign tumors such as meningiomas (n = 10) and pituitary adenomas (n = 5). A significant Treg increase in blood was seen only in patients with metastatic brain tumors. Tregs in high-grade tumors exhibited an activated phenotype as indicated by decreased proliferation and elevated CTLA-4 and FoxP3 expression relative to blood Tregs. Functional analysis showed that the tumor-derived Tregs efficiently suppressed cytokine secretion and proliferation of autologous intratumoral lymphocytes. Most tumor-infiltrating Tregs were localized in close proximity to effector T cells, as visualized by immunohistochemistry. Furthermore, 61% of the malignant brain tumors expressed programmed death ligand-1 (PD-L1), while the inhibitory PD-1 receptor was expressed on CD4+ effector cells present in 26% of tumors. In conclusion, using ultrasonic tumor aspirates as a biosource we identified Tregs and the PD-L1/PD-1 pathway as immune suppressive mechanisms in malignant but not benign human brain tumors.
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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.