bims-mesote 2026-08-16 papers

Issue of 2026–08–16
three papers selected by
Laura Mannarino, Humanitas Research

Chem Biol Interact. 2026 Aug 13. pii: S0009-2797(26)00410-2. [Epub ahead of print] 112302

ADRB2 Modulates Asbestos-Induced Pleural Mesothelioma Progression by Influencing IL-17/NF-κB-Related Inflammatory Signalling: An Integrated Network Toxicology, Multi-Omics and Experimental Study.

Shaoyang Huang, Dandan Gu, Jintao He, Guangsheng Hou, Jundong Wang, Zhengliang Li, Min Yu, Jiangyan Li, Wei Xiong.

Pleural mesothelioma (PM) is a highly aggressive asbestos-related malignancy with poor prognosis and limited early diagnostic options. In this study, network toxicology and integrated multi-omics analyses were used to investigate the molecular mechanisms by which chrysotile, crocidolite, and amosite may induce PM, and to identify diagnostic core genes. Asbestos-related targets from the Comparative Toxicogenomics Database (CTD) database were integrated with Gene Expression Omnibus (GEO) transcriptomic datasets, followed by differential expression analysis, weighted gene co-expression network analysis, protein-protein interaction analysis, functional enrichment, machine-learning screening, and SHAP interpretation. Candidate targets were mainly enriched in inflammation-related pathways, including cytokine regulation, complement and coagulation cascades, NF-κB, TNF, and IL-17 signalling. Adrenergic receptor beta 2 (ADRB2), LMO3, GPD1L, EDNRB, RNASE1, PDK4, CAT, and MAL showed strong diagnostic contributions, among which ADRB2 displayed particular mechanistic relevance. Immune-infiltration and single-cell RNA-sequencing analyses suggested that ADRB2 was associated with multiple immune-cell populations and was distributed across both malignant and immune-cell compartments within the PM microenvironment, while molecular docking indicated potential interactions between asbestos and multiple core proteins. LDH assays showed that 2.5 μg/cm2 represented a low-to-subtoxic exposure concentration in MeT-5A and MSTO-211H cells. At this concentration, all three asbestos types promoted proliferation, clonogenic growth, and invasion and up-regulated ADRB2, with crocidolite exerting the strongest effect. Mechanistically, ADRB2 knockdown attenuated crocidolite-induced IL-17/NF-κB-related signalling, reduced IL-6, CXCL1, and CXCL8 expression, and suppressed the malignant phenotype of MSTO-211H cells, whereas recombinant human IL-17A partially restored these effects. These findings identify ADRB2 as a potential diagnostic and mechanistic target in asbestos-related PM and suggest that ADRB2 may contribute to crocidolite-induced malignant progression by modulating cellular responses associated with IL-17/NF-κB-related inflammatory signalling.

Keywords: Adrenergic receptor beta 2 (ADRB2); Asbestos; IL-17/NF-κB-related inflammatory signalling; machine learning; network toxicology; pleural mesothelioma (PM)

DOI: https://doi.org/10.1016/j.cbi.2026.112302

Cancer Drug Resist. 2026 ;9 24

Lack of resolution of inflammation marks malignant pleural mesothelioma progression.

Veronica Gatti, Matti van Welzen, Alessandro Napoli, Marc Dubourdeau, Marta Tiberi, Andrea Marra, Giorgia Giorgi, Clémence Gély, Veronica Ceci, Olaf Wolkenhauer, Tommaso Mazza, Shailendra Gupta, Mario Cioce, Valerio Chiurchiù, Vito Michele Fazio.

Aim: Malignant pleural mesothelioma (MPM) is a paradigmatic inflammation-associated cancer and a major therapeutic challenge due to its resistance to treatment. Inflammation is thought to promote both tumor progression and therapy resistance. Senescence-associated secretory phenotype (SASP)-mediated, chemotherapy-induced release of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) contributes to pemetrexed resistance in MPM cells in vitro. Methods: Pro-inflammatory mediators (PIMs) and specialized pro-resolving mediators (SPMs) were quantified in pleural exudates using liquid chromatography-tandem mass spectrometry. Single-cell RNA-sequencing datasets were analyzed to assess the distribution of SPM-producing enzymes between mesothelial and mesothelioma cells in both tumor tissue and uninvolved pleura. Least Absolute Shrinkage and Selection Operator regression (LASSO) was used to derive a composite prognostic score (CPS) from SPM-related gene expression. Results: Chemotherapy-treated patients exhibited a reduction in SPMs - including resolvins, protectins, and maresins - alongside increased prostaglandin levels. Single-cell analysis revealed differential partitioning of SPM-producing enzymes, with lower expression in mesothelioma cells compared with mesothelial cells. A five-gene CPS derived from this lipid mediator landscape independently predicted overall survival beyond conventional clinical parameters. Conclusion: Chemotherapy alters the lipid mediator composition of pleural exudates in MPM by reducing SPMs, thereby disrupting resolution pathways. This effect is consistent with an intrinsic imbalance in expression between mesothelial and mesothelioma cells. Together, these findings suggest that impaired resolution of inflammation contributes to a pro-tumorigenic, pro-inflammatory, and chemoresistant microenvironment in MPM, with potential prognostic implications.

Keywords: Specialized pro-resolving mediators; chemoresistance; inflammation resolution; lipidomics; mesothelioma

DOI: https://doi.org/10.20517/cdr.2026.33

J Thorac Dis. 2026 Jul 31. 18(7): 731

Retrospective cohort study on prognostic factors of malignant pleural effusion secondary to pleural mesothelioma.

Xin Qiao, Jing-Jing Zhang, Bin Liu, Jian-Wen Qin.

Background: Malignant pleural effusion (MPE) frequently complicates pleural mesothelioma; however, prognostic determinants for this condition, particularly pleural fluid biomarkers, have yet to be comprehensively characterized. This study sought to assess the prognostic utility of clinical profiles and laboratory findings, with a specific focus on pleural fluid parameters, in patients with mesothelioma-associated MPE.
Methods: This retrospective cohort study included patients diagnosed with MPE secondary to pleural mesothelioma at Tianjin Chest Hospital from January 2015 to May 2025. Inclusion criteria: age ≥18 years, confirmed diagnosis. Exclusion criteria: active infection, incomplete baseline clinical/laboratory data, or prior anti-tumor therapy. Follow-up was conducted via telephone at monthly intervals for 6 months then every 3 months. The primary outcome was overall survival (OS), defined as time from diagnosis to death or last follow-up. Univariable and multivariable Cox regression analyses were performed to identify independent prognostic factors.
Results: Seventy‑one eligible patients were analyzed. Median OS was 30 months (range, 16-44 months). Four factors were independently associated with OS in multivariable analysis: pleural fluid lactate dehydrogenase (LDH) ≥361 U/L [hazard ratio (HR) 4.373, 95% confidence interval (CI): 1.903-10.049, P=0.001], fibrinogen (FIB) ≥3.82 g/L (HR 3.592, 95% CI: 1.683-7.666, P=0.001), mean platelet volume (MPV) ≥12.50 fL (HR 2.507, 95% CI: 1.125-5.586, P=0.03), and absolute lymphocyte count ≥1.48×109/L (HR 0.423, 95% CI: 0.204-0.877, P=0.02).
Conclusions: These four routinely available baseline parameters-pleural fluid LDH, FIB, MPV, and absolute lymphocyte count-may serve as potential prognostic indicators in patients with MPE secondary to pleural mesothelioma. Prospective, multicenter studies with external validation are required to confirm these findings.

Keywords: Malignant pleural effusion (MPE); overall survival (OS); pleural fluid biomarkers; pleural mesothelioma; prognosis

DOI: https://doi.org/10.21037/jtd-2026-0776