ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
Advanced Age Increases Immunosuppression in the Brain and Decreases Immunotherapeutic Efficacy in Subjects with Glioblastoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.
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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
74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 108 citations in OpenAlex.
- Glioblastoma immunotherapy in the context of the aging immune system: a systematic review and meta-analysis.Journal of neuro-oncology · 2026Pooled it
- Impact of molecular and clinical variables on survival outcome with immunotherapy for glioblastoma patients: A systematic review and meta-analysis.CNS neuroscience & therapeutics · 2022Pooled it
- Targeting immunosuppressive network in glioblastoma: Emerging strategies to overcome immunodeficiency and enhance therapeutic efficacy.Acta pharmaceutica Sinica. B · 2026Review
- Identification of an age-related monocyte-derived macrophages characteristic genes-based signature for high-grade diffuse glioma.Scientific reports · 2026Article
- Opposing functions of white matter in glioblastoma.Neuro-oncology · 2026Article
- Magnetic susceptibility properties of tumor-associated cells imaged by MRI reveal glioblastoma infiltration in the edema region.Communications medicine · 2025Article
- Ageing, immune fitness and cancer.Nature reviews. Cancer · 2025Review
- The glioma microenvironment and its impact on antitumor immunity.Neuro-oncology advances · 2025Review
- Effects of aging on anticancer therapy in murine cancer models.Cancer metastasis reviews · 2025Review
- Tryptophan metabolism: From physiological functions to key roles and therapeutic targets in cancer (Review).Oncology reports · 2025Review
- Socioeconomic influences on survival outcome in idh-wildtype glioma patients: examining the role of age, education, and lifestyle factors.Acta neurochirurgica · 2025Article
- Development and validation of nomogram model predicting overall survival and cancer specific survival in glioblastoma patients.Discover oncology · 2025Article
- Heterogeneity in pericyte inflammatory responses across age and species highlight the importance of human cell models.Molecular brain · 2025Article
- Recent Advances in Nanoenzymes Based Therapies for Glioblastoma: Overcoming Barriers and Enhancing Targeted Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Rational Design and Optimization of a Potent IDO1 Proteolysis Targeting Chimera (PROTAC).Journal of medicinal chemistry · 2025Article
- Knockout IL4I1 affects macrophages to improve poor efficacy of CD19 CAR-T combined with PD-1 inhibitor in relapsed/refractory diffuse large B-cell lymphoma.Journal of translational medicine · 2025Article
- Comparative analysis of deep learning and radiomic signatures for overall survival prediction in recurrent high-grade glioma treated with immunotherapy.Cancer imaging : the official publication of the International Cancer Imaging Society · 2025Article
- Is modulation of immune checkpoints on glioblastoma-infiltrating myeloid cells a viable therapeutic strategy?Neuro-oncology · 2025Review
- Immune intrinsic escape signature stratifies prognosis, characterizes the tumor immune microenvironment, and identifies tumorigenic PPP1R8 in glioblastoma multiforme patients.Frontiers in immunology · 2025Article
- Prognostic and predictive determinants in high-grade gliomas: integrating tumor-intrinsic biology with patient and system-level factors.Frontiers in neurology · 2025Review
14 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
25 authors at 9 institutions in 4 countries.
Funding
Abstract
purposeWild-type isocitrate dehydrogenase-expressing glioblastoma (GBM) is the most common and aggressive primary brain tumor with a median age at diagnosis of ≥65 years. It accounts for approximately 90% of all GBMs and has a median overall survival (OS) of <15 months. Although immune checkpoint blockade (ICB) therapy has achieved remarkable survival benefits in a variety of aggressive malignancies, similar success has yet to be achieved for GBM among phase III clinical trials to date. Our study aimed to understand the relationship between subject age and immunotherapeutic efficacy as it relates to survival from glioma. EXPERIMENTAL
design(i) Clinical data: GBM patient datasets from The Cancer Genome Atlas, Northwestern Medicine Enterprise Data Warehouse, and clinical studies evaluating ICB were stratified by age and compared for OS. (ii) Animal models: young, middle-aged, and older adult wild-type and indoleamine 2,3 dioxygenase (IDO)-knockout syngeneic mice were intracranially engrafted with CT-2A or GL261 glioma cell lines and treated with or without CTLA-4/PD-L1 mAbs, or radiation, anti-PD-1 mAb, and/or a pharmacologic IDO enzyme inhibitor.
resultsAdvanced age was associated with decreased GBM patient survival regardless of treatment with ICB. The advanced age-associated increase of brain IDO expression was linked to the suppression of immunotherapeutic efficacy and was not reversed by IDO enzyme inhibitor treatment.
conclusionsImmunosuppression increases in the brain during advanced age and inhibits antiglioma immunity in older adults. Going forward, it will be important to fully understand the factors and mechanisms in the elderly brain that contribute to the decreased survival of older patients with GBM during treatment with ICB.
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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.