ArticleJCI insight2022
MCP-1/CCR2 axis inhibition sensitizes the brain microenvironment against melanoma brain metastasis progression.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Unraveling the Enigma of Melanoma Brain Metastasis: New Molecular Insights and Therapeutic Directions.International journal of molecular sciences · 2026Review
- miRNA-driven cancer cell plasticity, tolerance and therapy resistance: lessons from melanoma.Molecular cancer · 2026Review
- Diversity and function of tumor-associated macrophages in brain metastases: mechanisms and therapeutic prospects.Frontiers in immunology · 2026Review
- p53 inactivation drives breast cancer metastasis to the brain through SCD1 upregulation and increased fatty acid metabolism.Nature genetics · 2026Article
- SPP1+ macrophages polarized by lactate confer the progression of hypoxic adaptive tumor cells in brain.Neuro-oncology · 2026Article
- Article
- Tumor suppressors in Sox2-mediated lung cancers promote distinct cell-intrinsic and immunologic remodeling.JCI insight · 2025Article
- CCL2 blockade combined with PD-1/P-selectin immunomodulators impedes breast cancer brain metastasis.Brain : a journal of neurology · 2025Article
- Regulation of metastatic organotropism.Trends in cancer · 2025Review
- The role of monocytes and macrophages in the progression of Alzheimer's disease.Frontiers in immunology · 2025Review
- Current preclinical models of brain metastasis.Clinical & experimental metastasis · 2024Review
- Association between inflammatory factors and melanoma: a bidirectional Mendelian randomization study.Cancer causes & control : CCC · 2024Article
- Correlation of Immunomodulatory Cytokines with Tumor Volume and Cerebrospinal Fluid in Vestibular Schwannoma Patients.Cancers · 2024Article
- Tumor cell-intrinsic MELK enhanced CCL2-dependent immunosuppression to exacerbate hepatocarcinogenesis and confer resistance of HCC to radiotherapy.Molecular cancer · 2024Article
- Phase II trial of pembrolizumab, ipilimumab, and aspirin in melanoma: clinical outcomes and translational predictors of response.BJC reports · 2024Article
- Integration analysis of single-cell transcriptome reveals specific monocyte subsets associated with melanoma brain and leptomeningeal metastasis.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2024Article
- The Role of Microglia in Brain Metastases: Mechanisms and Strategies.Aging and disease · 2024Review
- Immune escape and metastasis mechanisms in melanoma: breaking down the dichotomy.Frontiers in immunology · 2024Review
- Harnessing immunotherapy for brain metastases: insights into tumor-brain microenvironment interactions and emerging treatment modalities.Journal of hematology & oncology · 2023Review
- Regulation and Function of CCL2 and N-Myc in Retinoic Acid-treated Neuroblastoma Cells.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Development of resistance to chemo- and immunotherapies often occurs following treatment of melanoma brain metastasis (MBM). The brain microenvironment (BME), particularly astrocytes, cooperate toward MBM progression by upregulating secreted factors, among which we found that monocyte chemoattractant protein-1 (MCP-1) and its receptors, CCR2 and CCR4, were overexpressed in MBM compared with primary lesions. Among other sources of MCP-1 in the brain, we show that melanoma cells altered astrocyte secretome and evoked MCP-1 expression and secretion, which in turn induced CCR2 expression in melanoma cells, enhancing in vitro tumorigenic properties, such as proliferation, migration, and invasion of melanoma cells. In vivo pharmacological blockade of MCP-1 or molecular knockout of CCR2/CCR4 increased the infiltration of cytotoxic CD8+ T cells and attenuated the immunosuppressive phenotype of the BME as shown by decreased infiltration of Tregs and tumor-associated macrophages/microglia in several models of intracranially injected MBM. These in vivo strategies led to decreased MBM outgrowth and prolonged the overall survival of the mice. Our findings highlight the therapeutic potential of inhibiting interactions between BME and melanoma cells for the treatment of this disease.
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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.