ArticleCell reports. Medicine2024
Spatial transcriptomics analysis identifies a tumor-promoting function of the meningeal stroma in melanoma leptomeningeal disease.
Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Integrated Genomic and Proteomic Analysis Reveals T-B Lymphocyte Signatures in the MYCN Driven "Immune Desert" of Specific Neuroblastoma Subtypes.CNS neuroscience & therapeutics · 2026Article
- Meningeal-tumor interactions define distinct modes of leptomeningeal colonization in Group 3 medulloblastoma.Acta neuropathologica communications · 2026Article
- Spatial transcriptomics and single-cell analyses reveal the role of the cisplatin-resistant gene panel in NSCLC progression and the tumor microenvironment, identifying LOXL2 as a potential therapeutic target.Cancer cell international · 2026Article
- Mechanisms of the Antiproliferative Effects of SIRT6 Inhibition in Melanoma: A Multi-Omics Analysis.Cancers · 2026Article
- Advancing precision immuno-oncology in melanoma: the synergistic convergence of personalized neoantigen vaccines and multi-omics biomarker profiling.Frontiers in immunology · 2026Review
- Current and emerging strategies for the management of brain and leptomeningeal metastases in melanoma.Frontiers in oncology · 2026Review
- Dynamic changes of synergy relationship between lncRNA and immune checkpoint in cancer progression.Briefings in bioinformatics · 2025Article
- spatialGE Is a User-Friendly Web Application That Facilitates Spatial Transcriptomics Data Analysis.Cancer research · 2025Article
- Reimagining the meninges from a neuroimmune perspective: a boundary, but not peripheral.Journal of neuroinflammation · 2024Review
- spatialGE: A user-friendly web application to democratize spatial transcriptomics analysis.bioRxiv : the preprint server for biology · 2024Article
- The immune landscape of cerebrospinal fluid across brain malignancies.Neuro-oncology advancesReview
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Abstract
Leptomeningeal disease (LMD) remains a rapidly lethal complication for late-stage melanoma patients. Here, we characterize the tumor microenvironment of LMD and patient-matched extra-cranial metastases using spatial transcriptomics in a small number of clinical specimens (nine tissues from two patients) with extensive in vitro and in vivo validation. The spatial landscape of melanoma LMD is characterized by a lack of immune infiltration and instead exhibits a higher level of stromal involvement. The tumor-stroma interactions at the leptomeninges activate tumor-promoting signaling, mediated through upregulation of SERPINA3. The meningeal stroma is required for melanoma cells to survive in the cerebrospinal fluid (CSF) and promotes MAPK inhibitor resistance. Knocking down SERPINA3 or inhibiting the downstream IGR1R/PI3K/AKT axis results in tumor cell death and re-sensitization to MAPK-targeting therapy. Our data provide a spatial atlas of melanoma LMD, identify the tumor-promoting role of meningeal stroma, and demonstrate a mechanism for overcoming microenvironment-mediated drug resistance in LMD.
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