ArticleNature cell biology2024
Astrocyte-induced Cdk5 expedites breast cancer brain metastasis by suppressing MHC-I expression to evade immune recognition.
Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Proteogenomic analysis of the CALGB 40601 (Alliance) HER2+ breast cancer neoadjuvant trial reveals resistance biomarkers.Cell reports. Medicine · 2025Trial
- Review
- Re-expression of MHC-I to treat CNS cancers.Oncotarget · 2026Review
- Neural regulation of tumor immunity: emerging opportunities to enhance cancer immunotherapy.Experimental & molecular medicine · 2026Review
- Astrocyte heterogeneity in brain metastases.Molecular oncology · 2026Review
- ACSS2 Suppresses Ferroptosis to Drive Breast Cancer Brain Metastasis.Cancer research · 2026Article
- 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
- 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
- Cyclin-Dependent Kinase 5 Contributes to Bruton's Tyrosine Kinase Inhibitor Resistance via the IRE1α/XBP1 Axis in Mantle Cell Lymphoma.Research square · 2026Article
- Astrocyte-driven immunosuppression in the brain tumor microenvironment.Nature immunology · 2026Review
- Mitochondrial Fission and Fusion Disorders and Autophagy Abnormalities in Parkinson's Disease.Neurochemical research · 2026Review
- Targeting IL27RA Enhances Immunotherapy in Triple-Negative Breast Cancer by Modulating Tumor Cells and the Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Breast Cancer Brain Metastases: Current Understanding and Future Directions.Current oncology reports · 2026Review
- The evolving landscape of brain metastasis: volume II.Trends in cancer · 2026Review
- Cancer Neuroscience: Linking Neuronal Plasticity with Brain Tumor Growth and Resistance.Biology · 2026Review
- Low prognostic nutritional index score is associated with lymph node metastasis in patients with breast cancer, whereas hemoglobin-albumin-lymphocyte-platelet score is not.Frontiers in oncology · 2026Article
- A patent review of cyclin-dependent kinase 5 (CDK5) inhibitors (1999-2025).Frontiers in bioengineering and biotechnology · 2026Review
- Mechanism of zedoary turmeric oil multi-components targeting S100A14 to reprogram astrocytes against tumor brain metastasis.Frontiers in pharmacology · 2026Article
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
Brain metastases (BrMs) evade the immune response to develop in the brain, yet the mechanisms of BrM immune evasion remains unclear. This study shows that brain astrocytes induce the overexpression of neuronal-specific cyclin-dependent kinase 5 (Cdk5) in breast cancer-derived BrMs, which facilitates BrM outgrowth in mice. Cdk5-overexpressing BrMs exhibit reduced expression and function of the class I major histocompatibility complex (MHC-I) and antigen-presentation pathway, which are restored by inhibiting Cdk5 genetically or pharmacologically, as evidenced by single-cell RNA sequencing and functional studies. Mechanistically, Cdk5 suppresses MHC-I expression on the cancer cell membrane through the Irf2bp1-Stat1-importin α-Nlrc5 pathway, enabling BrMs to avoid recognition by T cells. Treatment with roscovitine-a clinically applicable Cdk5 inhibitor-alone or combined with immune checkpoint inhibitors, significantly reduces BrM burden and increases tumour-infiltrating functional CD8
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