ArticleThe Journal of clinical investigation2021
SLIT2/ROBO signaling in tumor-associated microglia and macrophages drives glioblastoma immunosuppression and vascular dysmorphia.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.
What it found
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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
82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 109 citations in OpenAlex.
- mRNA markers for survival prediction in glioblastoma multiforme patients: a systematic review with bioinformatic analyses.BMC cancer · 2024Pooled it
- Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes.Nature communications · 2023Pooled it
- Human Papillomavirus (HPV)-Infected Epithelial Cells and FBLN1-Positive Fibroreticular Cells Govern the Immunogenic Tumor Microenvironment in HPV-Associated Oropharyngeal Squamous Cell Carcinoma.Clinical and experimental otorhinolaryngology · 2026Article
- Neural regulation of tumor immunity: emerging opportunities to enhance cancer immunotherapy.Experimental & molecular medicine · 2026Review
- Integrative bioinformatics analysis unveils neuro-cancer crosstalk-related genes and establishes prognostic risk model in Glioblastoma.Scientific reports · 2026Article
- CD47 stabilizes ROBO2 to regulate glioblastoma progression by preventing ITCH-mediated ubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Identification of SLIT3 mutation as a response biomarker for immune checkpoint inhibitor therapy in non-small cell lung cancer.Discover oncology · 2026Article
- Dissecting the aberrant vasculature of glioblastoma: mechanisms and therapeutic targets.Cancer metastasis reviews · 2026Review
- Frizzled-1 amplification promotes fibrosis in the gastric tumor microenvironment through the activation of fibroblasts via the SLIT2/ROBO1 axis.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Distinct molecular pathways leading to dosage-dependent temozolomide resistance in GBM stem cells.Cancer cell international · 2026Article
- Neuronal guidance signaling in neurodegenerative diseases: Key regulators that function at neuron-glia and neuroimmune interfaces.Neural regeneration research · 2026Article
- Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Article
- Exposure-aware multi-omics and artificial intelligence for biomarker discovery and precision prevention in diffuse glioma.Frontiers in immunology · 2026Review
- Discovery of a first-in-class SLIT2 binder disrupting the SLIT2/ROBO1 axisRSC medicinal chemistry · 2025Article
- Glioblastoma insights: Focus on crosstalk with the suppressive tumor microenvironment and advanced therapeutic strategies.Medicine · 2025Review
- Construction of an eight-basement membrane related gene signature for predicting prognosis and immune response in hepatocellular carcinoma.Discover oncology · 2025Article
- A Multi-omics Exploration Revealing SLIT2 as a Prime Therapeutic Target for Peripheral Facial Paralysis: Integrating Single-Cell Transcriptomics and Plasma Proteome Data.Cellular and molecular neurobiology · 2025Article
- Review
- Common and distinct circulating microRNAs in four neurovascular disorders.Biochemistry and biophysics reports · 2025Article
22 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 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SLIT2 is a secreted polypeptide that guides migration of cells expressing Roundabout 1 and 2 (ROBO1 and ROBO2) receptors. Herein, we investigated SLIT2/ROBO signaling effects in gliomas. In patients with glioblastoma (GBM), SLIT2 expression increased with malignant progression and correlated with poor survival and immunosuppression. Knockdown of SLIT2 in mouse glioma cells and patient-derived GBM xenografts reduced tumor growth and rendered tumors sensitive to immunotherapy. Tumor cell SLIT2 knockdown inhibited macrophage invasion and promoted a cytotoxic gene expression profile, which improved tumor vessel function and enhanced efficacy of chemotherapy and immunotherapy. Mechanistically, SLIT2 promoted microglia/macrophage chemotaxis and tumor-supportive polarization via ROBO1- and ROBO2-mediated PI3K-γ activation. Macrophage Robo1 and Robo2 deletion and systemic SLIT2 trap delivery mimicked SLIT2 knockdown effects on tumor growth and the tumor microenvironment (TME), revealing SLIT2 signaling through macrophage ROBOs as a potentially novel regulator of the GBM microenvironment and immunotherapeutic target for 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.