What question did this study set out to answer?

The study aims to characterize the heterogeneity of malignant pleural mesothelioma using multimodal datasets.

April 5, 2026Cancer Research0 citations

Abstract 2711: Large-scale integration of single-nuclei and spatial transcriptomics from the ETOP BEAT-meso trial reveals clinically relevant heterogeneity in malignant pleural mesothelioma.

DBDaria BusztaSwiss Cancer Center Léman JBJonathan BacUniversity Hospital of Lausanne MNMaxim NorkinSwiss Cancer Center Léman

Key Points

The study aims to characterize the heterogeneity of malignant pleural mesothelioma using multimodal datasets.
Analyzed FFPE tissues from 159 patients enrolled in the BEAT-meso trial.
Generated largest multimodal MPM dataset, including single-nuclei RNA-seq, spatial transcriptomics, and clinical data.
Built a snRNA-seq atlas through preprocessing and hierarchical cell type annotations.
Stratified clinical variables to assess variations in cellular composition.
Used foundation models to learn multimodal representations across collected data.
Identified differences in cell-type composition and pathway activity between epithelioid and non-epithelioid tumors.
Found sarcomatoid-like molecular signatures indicating heterogeneity beyond standard classifications.
Characterized malignant cell states refined through transcriptomic program analysis.
Confirmed localization of diverse cell types using spatial transcriptomics.

Abstract

Abstract Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the lung lining, predominantly caused by asbestos exposure (1,2). Despite advancing therapies, 5-year survival remains poor at 10-20% (3,4). A major challenge in managing MPM is its extensive heterogeneity, which contributes to variable treatment response. Comprehensive characterisation of this heterogeneity may help guide more effective therapies. Meeting this need requires large-scale, multimodal datasets that capture the cellular, spatial and molecular landscape of MPM. We analysed FFPE tissues from 159 patients enrolled in the BEAT-meso trial (5), generating the largest multimodal MPM dataset from a single clinical trial. The dataset includes paired single-nuclei FLEX RNA-seq (snRNA-seq; 612,587 cells), spatial Xenium transcriptomics (37,949,307 cells), H Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2711.

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