bims-mesote 2026-09-06 papers

Issue of 2026–09–06
four papers selected by
Laura Mannarino, Humanitas Research

Front Oncol. 2026 ;16 1883870

Multi-omics integration in malignant pleural mesothelioma: from molecular evolution and immune ecosystems to precision therapy.

Hongmei Li, Kunzhong Zhou, Ruiting Xu, Weifang Wang, Tingting Song, Yonghong Zhou, Jing Ren, Zhiyong Wang, Yiteng Liang, Yilin Chen, Saurav Poudel, Junxuan Yu, Rui Lin, Ke Yin, Shengjie Yang, Li Zhuang.

Malignant pleural mesothelioma (MPM) exhibits substantial molecular and cell-state heterogeneity, together with marked spatial variation in its immune and stromal microenvironment. Histological classification and individual biomarkers alone cannot adequately explain its evolution or heterogeneous treatment responses. This review critically integrates genomic, epigenomic, transcriptomic, single-cell, and spatial omics evidence along a conceptual continuum encompassing tumor-intrinsic molecular evolution, microenvironmental ecosystem remodeling, candidate stratification, and precision therapy. Current evidence indicates that alterations involving BAP1, CDKN2A/MTAP, and the NF2/Hippo pathway impose evolutionary constraints and create candidate therapeutic vulnerabilities but are insufficient to determine functional phenotypes independently. Epithelioid, uncommitted, and sarcomatoid malignant cell states may coexist within the same genetic clone, while immune and stromal features display pronounced regional heterogeneity. Based on published human MPM cohorts, we further propose four provisional immune-ecosystem archetypes: T-cell-inflamed, B-cell/tertiary lymphoid structure-organized, myeloid-dominant, and immune-desert. Tumor-intrinsic molecular states and stromal-spatial features are treated as interpretive modifiers. This literature-derived framework is intended for hypothesis generation and has not been developed or validated as a clinical classifier. At present, the principal value of multi-omics lies in mechanistic discovery and the design of biomarker-enriched clinical trials. Future studies should employ standardized assays in multicenter cohorts, independent external validation, formal archetype-by-treatment interaction testing within randomized trials, and longitudinal sampling to determine the treatment-predictive value and clinical feasibility of this framework.

Keywords: immune ecosystem stratification; malignant pleural mesothelioma; multi-omics; precision therapy; single-cell sequencing; spatial omics; tumor microenvironment

DOI: https://doi.org/10.3389/fonc.2026.1883870

Tissue Cell. 2026 Aug 22. pii: S0040-8166(26)00584-7. [Epub ahead of print]104(Pt 2): 103889

Thonzonium bromide suppresses malignant phenotypes of pleural mesothelioma cells in association with reduced KAP1 Ser473 phosphorylation.

Dan Song, Jintao He, Qianwen Du, Shaoyang Huang, Wenbing Huang, Zhengliang Li, Zifeng Ruan, Xingguo Liu, Jing Zhang, Wei Xiong.

OBJECTIVE: Pleural mesothelioma (PM) is an aggressive thoracic malignancy with limited therapeutic options. This study investigated the biological role of KAP1 in PM and explored the relationship between thonzonium bromide (TB), KAP1 regulation, and malignant phenotypes of PM cells.
METHODS: KAP1 expression in PM was evaluated using public databases, RT-qPCR, western blotting, and immunohistochemistry. KAP1 was depleted in MSTO-211H and NCI-H2452 cells, and cellular viability, proliferation, migration, and invasion were assessed. TB-associated and PM-related targets were compared, followed by molecular docking, molecular dynamics (MD) simulation, and cellular thermal shift assay (CETSA). Dose-response and time-response experiments were used to determine an appropriate TB concentration. Site-specific KAP1 phosphorylation and selected ERK1/2, p38 MAPK and apoptosis-related proteins were examined by western blotting. Genetic interaction experiments combining KAP1 depletion and TB treatment were also performed.
RESULTS: KAP1 was elevated in PM tissue samples and cell lines, and higher expression was associated with shorter overall survival in unadjusted survival analysis. KAP1 depletion suppressed malignant phenotypes of PM cells. Fifty-one overlapping TB-associated and PM-associated targets were identified. Molecular docking predicted a potential TB-KAP1 interaction with a docking score of -6.3 kcal/mol, and molecular dynamics simulation indicated conformational stability of the predicted complex. CETSA showed increased thermal stability of KAP1 following TB treatment, supporting intracellular target engagement. TB at 1 μM for 48 h significantly inhibited both MSTO-211H and NCI-H2452 cell lines while exerting relatively limited effects on non-malignant MeT-5A cells. TB reduced the pSer473-KAP1/total KAP1 ratio in a concentration-dependent manner and suppressed proliferation, migration, and invasion. KAP1 depletion and TB treatment produced partially overlapping inhibitory effects, accompanied by altered ERK1/2 and p38 MAPK phosphorylation and increased levels of cleaved caspase-3 and cleaved PARP.
CONCLUSIONS: TB suppresses the malignant phenotypes of PM cells in vitro, while CETSA supports intracellular engagement of KAP1, accompanied by reduced pSer473-KAP1. These findings suggest that KAP1 contributes to the cellular response to TB, although KAP1-independent mechanisms may also be involved. Further phosphosite-specific and in vivo studies are warranted to clarify the underlying mechanism and translational potential.

Keywords: Invasion and migration; KRAB‑associated protein 1 (KAP1); Molecular docking; Molecular dynamics simulation; Pleural mesothelioma (PM); Proliferation; Thonzonium bromide (TB)

DOI: https://doi.org/10.1016/j.tice.2026.103889

Respirol Case Rep. 2026 Sep;14(9): e70734

Sarcomatoid Mesothelioma Revealed After Treatment for Tuberculous Pleurisy: A Case Report.

Daiki Nagayama, Keiki Yokoo, Yousuke Yabushita, Motoki Sekikawa, Masaru Abe, Hiroaki Kato, Ayumi Takayanagi, Bunya Takahashi, Marie Kato-Shinomiya, Satoshi Ota, Gen Yamada, Kenzo Hiroshima, Hirofumi Chiba.

Differentiating tuberculous (TB) pleurisy from malignant pleural mesothelioma is challenging due to similar clinical presentations. We report an 83-year-old man with sarcomatoid mesothelioma initially treated for TB pleurisy. He presented with lymphocyte-predominant exudative pleural effusion and a positive Interferon-Gamma Release Assay. Thoracoscopy revealed purulent effusion, but biopsies were non-diagnostic. Despite empiric anti-tuberculosis therapy, the effusion persisted. A subsequent surgical biopsy showed fibrosis and scattered spindle cells. However, 2 months later, a rapidly growing chest wall mass with bone invasion appeared. A CT-guided percutaneous biopsy showed proliferation of atypical spindle cells and fluorescence in situ hybridization (FISH) analysis allowed for the diagnosis of sarcomatoid mesothelioma. This case highlights the aggressive nature of sarcomatoid mesothelioma and its diagnostic difficulty. For treatment-refractory pleurisy, clinicians must maintain high suspicion, ensuring vigilant follow-up and prompt repeat biopsies despite negative initial results, while consulting pathologists to consider additional FISH testing.

Keywords: fluorescence in situ hybridization (FISH); pleural biopsy; sarcomatoid mesothelioma; tuberculous pleurisy

DOI: https://doi.org/10.1002/rcr2.70734

Lung Cancer. 2026 Aug 26. pii: S0169-5002(26)00653-7. [Epub ahead of print]220 109592

Environmental asbestos exposure and lung cancer burden compared with mesothelioma in rural Türkiye: A 33-Year population-based cohort study.

Guntulu Ak, Selma Metintas, Nico van Zandwijk, Muzaffer Metintas.

BACKGROUND: Long-term environmental asbestos exposure remains an underrecognized cause of lung cancer (LC). We evaluated the impact of environmental asbestos exposure on LC mortality, temporal trends, years of life lost (YLL), and its relationship with malignant mesothelioma in a 33-year population-based cohort in rural Türkiye.
METHODS: This retrospective cohort included all LC and mesothelioma cases diagnosed between 1990 and 2022 in environmentally asbestos-exposed and adjacent non-exposed districts in Eskişehir region of Central Anatolia. Age-standardized mortality rates, Joinpoint trend analyses, relative risks (RRs), and YLL were calculated using person-year denominators.
RESULTS: The cohort comprised 1,223,765 exposed and 388,401 non-exposed person-years. Overall, 629 LC cases were identified in exposed districts and 46 in non-exposed districts, whereas 235 malignant mesothelioma cases occurred only in exposed districts. Environmental asbestos exposure increased LC mortality more than fourfold (RR, 4.11; 95% CI, 3.02-5.60). Age-standardized LC mortality rates were 71.5 and 8.8 per 100,000 person-years among exposed men and women, versus 19.0 and 0.85, respectively, in non-exposed populations. LC mortality increased over time (annual percentage change, 6.8% in men and 13.0% in women). LC mortality exceeded mesothelioma mortality 2.68-fold and accounted for greater YLL, whereas clinicopathological characteristics and survival were similar between groups.
CONCLUSIONS: Long-term environmental asbestos exposure substantially increases LC mortality and premature mortality. Although mesothelioma remains the sentinel asbestos-related malignancy, LC represents the principal population-level consequence of environmental asbestos exposure. These findings support incorporating environmental asbestos exposure into risk assessment, surveillance, and low-dose computed tomography screening strategies in endemic regions.

Keywords: Asbestos; Cohort Studies; Environmental Exposure; Lung Neoplasms; Mesothelioma; Mortality

DOI: https://doi.org/10.1016/j.lungcan.2026.109592