ArticleCancer discovery2023
Targeting Microglial Metabolic Rewiring Synergizes with Immune-Checkpoint Blockade Therapy for Glioblastoma.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Squalene Epoxidase: Its Regulations and Links with Cancers.International journal of molecular sciences · 2024Pooled it
- Research on tissue-resident macrophages in the field of cancer research: a bibliometric analysis from 2004 to 2025.Cell adhesion & migration · 2026Review
- Artificial intelligence-guided discovery of fungal ergosterol derivatives as selective LXRβ agonists targeting the cholesterol dependency of glioblastoma.Molecular diversity · 2026Article
- Neutrophil extracellular traps drive local tumor progression and metastasis following thermal ablation in liver cancer via TLR9-mediated inflammatory feedback and immunosuppression.Journal for immunotherapy of cancer · 2026Article
- Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment.Cellular & molecular immunology · 2026Review
- Humanized Murine Glioblastoma Models for Evaluation of Coxsackievirus Oncolytic Therapy.Cancers · 2026Article
- Oncolytic virus M1 reinvigorates CD8Cellular & molecular immunology · 2026Article
- Inhibiting macrophage-derived lactate transport restores cGAS-STING signalling and enhances antitumour immunity in glioblastoma.Nature cell biology · 2026Article
- Metabolic reprogramming and immunosenescence: a new sight for glioma therapy.Frontiers in cell and developmental biology · 2026Review
- Targeting lineage-specific heterogeneity and hypovascular-fibrotic barriers may enable precision immunotherapy in pituitary neuroendocrine tumors.Frontiers in immunology · 2026Review
- Exposure-aware multi-omics and artificial intelligence for biomarker discovery and precision prevention in diffuse glioma.Frontiers in immunology · 2026Review
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Reshaping the immunosuppressive glioma microenvironment: mechanisms, biomarkers, and emerging immunotherapies.Frontiers in immunology · 2026Review
- Next-generation immunotherapy biologics for glioblastoma.Frontiers in immunology · 2026Review
- Formation and remodeling of immunological niches in solid tumors: organ-specific architectures, inflammatory parallels, and therapeutic reprogramming.Frontiers in immunology · 2026Review
- ACT001 synergizes with temozolomide-based chemoradiotherapy to cure refractory glioblastoma by targeting TNF-CXCL10-CD8Frontiers in pharmacology · 2026Article
- SPP1+ macrophages polarized by lactate confer the progression of hypoxic adaptive tumor cells in brain.Neuro-oncology · 2026Article
- Progenitor cells, microglia, and non-coding RNAs: Orchestrators of glioblastoma pathogenesis and therapeutic resistance.Non-coding RNA research · 2025Review
- Biology of stem cell paradox: a double-edged sword-implications for cancer therapy.Cancer cell international · 2025Review
- Cut the fat: targeting cholesterol and lipid metabolism in glioblastoma.Cell death & disease · 2025Review
5 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
28 authors at 11 institutions in 6 countries.
Funding
Abstract
Glioblastoma (GBM) constitutes the most lethal primary brain tumor for which immunotherapy has provided limited benefit. The unique brain immune landscape is reflected in a complex tumor immune microenvironment (TIME) in GBM. Here, single-cell sequencing of the GBM TIME revealed that microglia were under severe oxidative stress, which induced nuclear receptor subfamily 4 group A member 2 (NR4A2)-dependent transcriptional activity in microglia. Heterozygous Nr4a2 (Nr4a2+/-) or CX3CR1+ myeloid cell-specific Nr4a2 (Nr4a2fl/flCx3cr1Cre) genetic targeting reshaped microglia plasticity in vivo by reducing alternatively activated microglia and enhancing antigen presentation capacity for CD8+ T cells in GBM. In microglia, NR4A2 activated squalene monooxygenase (SQLE) to dysregulate cholesterol homeostasis. Pharmacologic NR4A2 inhibition attenuated the protumorigenic TIME, and targeting the NR4A2 or SQLE enhanced the therapeutic efficacy of immune-checkpoint blockade in vivo. Collectively, oxidative stress promotes tumor growth through NR4A2-SQLE activity in microglia, informing novel immune therapy paradigms in brain cancer. SIGNIFICANCE: Metabolic reprogramming of microglia in GBM informs synergistic vulnerabilities for immune-checkpoint blockade therapy in this immunologically cold brain tumor. This article is highlighted in the In This Issue feature, p. 799.
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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.