ArticleMolecular cancer2023
Spatially resolved, high-dimensional transcriptomics sorts out the evolution of biphasic malignant pleural mesothelioma: new paradigms for immunotherapy.
Article in Molecular cancer, 2023. 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.
- Moving Beyond Morphology: Toward a Morpho-Molecular Classification of Pleural Mesothelioma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Review
- Multi-omics integration in malignant pleural mesothelioma: from molecular evolution and immune ecosystems to precision therapy.Frontiers in oncology · 2026Review
- Review
- CDKN2A deletion is associated with immune desertification in diffuse pleural mesothelioma.Journal of experimental & clinical cancer research : CR · 2025Article
- Digital spatial profiling for pathologists.Virchows Archiv : an international journal of pathology · 2025Article
- Mesothelioma cell heterogeneity identified by single cell RNA sequencing.Scientific reports · 2025Article
- The phenogenomic landscapes of pleural mesothelioma tumor microenvironment predict clinical outcomes.Journal of translational medicine · 2025Article
- Single-Cell View of Tumor Microenvironment Gradients in Pleural Mesothelioma.Cancer discovery · 2024Article
- Spatial Dissection of the Immune Landscape of Solid Tumors to Advance Precision Medicine.Cancer immunology research · 2024Review
- Review
- Cullin 4B Ubiquitin Ligase Is Important for Cell Survival and Regulates TGF-β1 Expression in Pleural Mesothelioma.International journal of molecular sciences · 2023Article
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8 authors.
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Abstract
backgroundMalignant Pleural Mesothelioma (MPM) is a dreadful disease escaping the classical genetic model of cancer evolution and characterized by wide heterogeneity and transcriptional plasticity. Clinical evolution of MPM is marked by a progressive transdifferentiation that converts well differentiated epithelioid (E) cells into undifferentiated and pleomorphic sarcomatoid (S) phenotypes. Catching the way this transition takes place is necessary to understand how MPM develops and progresses and it is mandatory to improve patients' management and life expectancy. Bulk transcriptomic approaches, while providing a significant overview, failed to resolve the timing of this evolution and to identify the hierarchy of molecular events through which this transition takes place.
methodsWe applied a spatially resolved, high-dimensional transcriptomic approach to study MPM morphological evolution. 139 regions across 8 biphasic MPMs (B-MPMs) were profiled using the GeoMx™Digital Spatial Profiler to reconstruct the positional context of transcriptional activities and the spatial topology of MPM cells interactions. Validation was conducted on an independent large cohort of 84 MPMs by targeted digital barcoding analysis.
resultsOur results demonstrated the existence of a complex circular ecosystem in which, within a strong asbestos-driven inflammatory environment, MPM and immune cells affect each other to support S-transdifferentiation. We also showed that TGFB1 polarized M2-Tumor Associated Macrophages foster immune evasion and that TGFB1 expression correlates with reduced survival probability.
conclusionsBesides providing crucial insights into the multidimensional interactions governing MPM clinical evolution, these results open new perspectives to improve the use of immunotherapy in this disease.
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