ArticleCancer discovery2025
TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells.
Article in Cancer discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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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
39 citing papers in PubMed.
- Review
- Advances in the role of astrocytes in glioma progression and therapy.Acta pharmacologica Sinica · 2026Review
- Lung Cancer Brain Metastasis: Brain Microenvironmental Adaptation, Therapeutic Resistance and Translational Strategies.Cancer science · 2026Review
- Re-expression of MHC-I to treat CNS cancers.Oncotarget · 2026Review
- Patient-derived resources for decoding and targeting brain metastases ecosystems.EMBO molecular medicine · 2026Review
- Astrocyte heterogeneity in brain metastases.Molecular oncology · 2026Review
- Mechanisms, Biomarkers, and Therapeutic Interventions of Neuroplasticity After Ischemic Stroke-A Scoping Review.Brain sciences · 2026Review
- MIF-Induced CD74+ Microglia and Macrophages Promote Progression of Brain Metastasis and Are Clinically Relevant across Central Nervous System Disorders.Cancer research · 2026Article
- Multiscale systems modelling of communication networks in brain metastasis.Experimental & molecular medicine · 2026Review
- Molecular mechanisms and therapeutic targets in lung cancer-nerve crosstalk.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Distinct immune landscapes characterize highly versus minimally invasive brain metastases.JCI insight · 2026Article
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Astrocyte-associated immunosuppressive programs in brain tumors: a STAT3-centered perspective.Cancer metastasis reviews · 2026Review
- Single-Cell Atlas of Renal Cell Carcinoma Brain Metastasis Uncovers Mechanisms of Immune Dysfunction and Resistance.bioRxiv : the preprint server for biology · 2026Article
- Astrocyte-driven immunosuppression in the brain tumor microenvironment.Nature immunology · 2026Review
- Targeting the neuro-immune crosstalk in breast cancer brain metastases.Journal for immunotherapy of cancer · 2026Review
- Astrocytes in neuroinflammation and brain cancer.Molecular biomedicine · 2026Review
- The Dual Roles of TIMP-1 in Cancer: From Protease Inhibition to Cytokine Signaling.Molecular biology reports · 2026Review
- The evolving landscape of brain metastasis: volume II.Trends in cancer · 2026Review
- Article
Corrections and comments
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Authors and funding
38 authors.
Funding
Abstract
Immunotherapies against brain metastases have shown clinical benefits when applied to asymptomatic patients, but they are largely ineffective in symptomatic cases for unknown reasons. Here, we dissect the heterogeneity in metastasis-associated astrocytes using single-cell RNA sequencing and report a population that blocks the antitumoral activity of infiltrating T cells. This protumoral activity is mediated by the secretion of tissue inhibitor of metalloproteinase-1 (TIMP1) from a cluster of pSTAT3+ astrocytes that acts on CD63+ CD8+ T cells to modulate their function. Using genetic and pharmacologic approaches in mouse and human brain metastasis models, we demonstrate that combining immune checkpoint blockade antibodies with the inhibition of astrocyte-mediated local immunosuppression may benefit patients with symptomatic brain metastases. We further reveal that the presence of tissue inhibitor of metalloproteinase-1 in liquid biopsies provides a biomarker to select patients for this combined immunotherapy. Overall, our findings demonstrate an unexpected immunomodulatory role for astrocytes in brain metastases with clinical implications. Significance: This study presents a significant advancement in understanding immune modulation in brain tumors and offers new insights into the potential therapeutic interventions for brain metastases. See related commentary by Lorger and James, p. 11.
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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 Socratic graph.