bims-mesote 2025-11-23 papers

Issue of 2025–11–23
five papers selected by
Laura Mannarino, Humanitas Research

Clin Exp Med. 2025 Nov 18. 26(1): 22

Comprehensive analysis reveals prognostic gene set that could impacts the response to chemotherapy and immunotherapy outcomes in malignant pleural mesothelioma.

Jun Li, Hongye He, Yutao Zhang, Muhammad Salman Azhar, Yongxiang Wang.

Malignant pleural mesothelioma (MPM) is a rare but aggressive thoracic malignancy primarily linked to asbestos exposure. Despite advances in research, the prognosis of MPM remains poor, and there is a lack of efficient and precise prognostic assessment tools. Its insidious onset, limited treatment options, and high resistance to therapy contribute to poor clinical outcomes and underscore the urgent need for reliable prognostic biomarkers. To address this gap, we integrated multi-omics data to identify a prognostic gene set for MPM and subsequently developed a prognostic model aiming to improve the clinical outcomes of this disease. Transcriptomic data from TCGA were used to identify genes related to prognosis and tumor stage in malignant pleural mesothelioma (MPM), followed by construction of a prognostic model via LASSO-Cox regression and external validation using a GEO dataset. The model was then integrated with DNA methylation and SNP data for GO enrichment analysis. Chemotherapy drug IC50 data from MPM cell lines were correlated with model gene expression to evaluate associations between risk scores and drug sensitivity, which were further validated using TCGA clinical response data. Finally, the model's impact on the immune microenvironment was assessed using single-cell RNA-seq data, and its predictive value for immunotherapy response was validated in an independent MPM immunotherapy cohort. Our novel prognostic model demonstrated consistent performance in both the training and validation cohorts. Patients with high-risk scores had poorer outcomes, with AUC values exceeding 0.8 and reaching 0.9 for 3 year survival prediction. The risk score accurately reflected biological processes such as tumor proliferation and metastasis in mesothelioma. It was also closely associated with clinical responses to radiotherapy and chemotherapy, with low-risk patients showing greater sensitivity and lower drug IC50 values. Additionally, the risk score correlated positively with tumor immune activity and was predictive of immunotherapy response. In conclusion, our prognostic model shows strong and reliable predictive power for patient survival and treatment response in malignant pleural mesothelioma. It not only reflects key tumor biological processes but also serves as a potential tool for guiding personalized therapy, including chemotherapy, radiotherapy, and immunotherapy.

Keywords: Chemotherapy; Malignant pleural mesothelioma; Prognosis; Tumor immunology

DOI: https://doi.org/10.1007/s10238-025-01949-9

Front Oncol. 2025 ;15 1671503

Case Report: IL-6 suppression: a potential strategy for mitigating severe immune-related adverse events in nivolumab and ipilimumab therapy for malignant pleural mesothelioma.

Asako Yanagisawa, Takumi Fukaya, Kento Noda, Hiroshi Kojima, Hidefumi Shimizu.

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer with a poor prognosis, often presenting challenges in treatment. The CheckMate-743 trial demonstrated significant improvements in overall survival with the combination therapy of nivolumab and ipilimumab in advanced MPM. However, the management of immune-related adverse events (irAEs) remains a critical concern.
Case presentation: We present a 74-year-old male with a history of polymyalgia rheumatica (PMR), diagnosed two years prior. His PMR was initially treated with corticosteroids, but tapering the dose was difficult. Therefore, tocilizumab was initiated one year before the current presentation, leading to a stable remission. One month before starting cancer therapy, tocilizumab was discontinued while the patient's PMR remained well-controlled. He then developed multiple serious irAEs following the first cycle of nivolumab and ipilimumab for advanced MPM. These included cytokine release syndrome (CRS), immune-related aseptic meningitis, and liver dysfunction. All irAEs were successfully managed with corticosteroids, and the patient's tumor progression remained under control.
Conclusion: This case suggests that residual IL-6 suppression from prior tocilizumab therapy may attenuate the severity of subsequent irAEs, permitting effective management without compromising anti-tumor efficacy. IL-6 modulation could be a promising strategy to improve the therapeutic index of dual checkpoint inhibition in MPM.

Keywords: IL-6; immune checkpoint inhibitor; immune-related adverse Events (irAEs); ipilimumab; malignant pleural mesothelioma; nivolumab; tocilizumab

DOI: https://doi.org/10.3389/fonc.2025.1671503

Pathologica. 2025 Sep;117(4): 366-373

Current approaches, barriers, and future directions in pleural mesothelioma diagnostics: results from an Italian National Survey.

Federica Pezzuto, Gianluca Lopez, Francesca Barbisan, Lorenzo Rosso, Giuseppe Pelosi, Mauro Papotti, Luisella Righi, Fiorella Calabrese.

Objective: This nationwide survey aimed to assess current diagnostic practices, adherence to international guidelines, and challenges encountered by Italian pathologists in the diagnosis of diffuse pleural mesothelioma (PM).
Methods: A structured questionnaire with 38 items was distributed electronically via Google Forms to Italian pathologists involved in mesothelioma diagnosis. Questions covered demographics, biopsy practices, pathology report, immunohistochemistry, molecular diagnostics, educational needs, and barriers to collaborative research.
Results: Participants represented diverse experience levels and institutional affiliations, primarily academic medical centers. Significant variability was found in tissue sampling and biobanking practices. Major diagnostic challenges included identifying sarcomatoid/desmoplastic patterns and inadequate adipose tissue in biopsies. Most pathologists managed inconclusive cases via multidisciplinary discussions and molecular analyses (BAP1, MTAP). Barriers identified included inadequate digital pathology infrastructure and limited standardized protocols for tissue collection. Participants strongly favored enhanced molecular resources, standardized histopathological protocols, and national collaborative initiatives.
Conclusions: Improved diagnostic accuracy requires targeted training, standardized protocols, enhanced molecular diagnostic capabilities, and structured national collaborations.

Keywords: diagnostic practices; histopathology; immunohistochemistry; molecular biomarkers; pleural mesothelioma

DOI: https://doi.org/10.32074/1591-951X-N1281

World J Clin Cases. 2025 Nov 16. 13(32): 110897

Positron emission tomography/computed tomography in risk-factor-negative young female with malignant pleural mesothelioma: A case report and review of literature.

Aikedan Aisikaer, Mo-Mo Sun, Jie Shen.

BACKGROUND: Malignant pleural mesothelioma (MPM), a rare aggressive malignancy, is primarily caused by asbestos exposure. MPM typically affects older adults (median age, 76 years), is uncommon in those under age 50 years and shows male predominance. Based on the American Society of Clinical Oncology guidelines, F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) is essential for initial MPM staging. Integrating quantitative FDG metabolic data with computed tomography (CT) anatomy optimizes biopsy accuracy and staging.
CASE SUMMARY: A 21-year-old female college student presented with fever (peak 38.4 °C), cough, and white mucoid sputum after cold exposure. Initial evaluation revealed elevated C-reactive protein [C-reactive protein (CRP); 65.52 mg/L] and Mycoplasma pneumoniae IgM. Despite resolution of fever following a 14-day moxifloxacin regimen, persistent cough prompted chest CT, which demonstrated left pleural mass-like thickenings. Levofloxacin therapy for 2 weeks failed to alleviate symptoms, accompanied by 2.5-kg weight loss over 1 month. Re-evaluation showed rising CRP (88.87 mg/L) with stable CT lesions, and negative T-cell spot test for tuberculosis and tumor markers. Contrast-enhanced CT revealed heterogeneously enhancing masses, while PET/CT detected two broad-based pleural lesions with intense FDG avidity. CT-guided biopsy confirmed epithelioid MPM. Thoracoscopy exposed diffuse fragile, hemorrhagic nodules implanting on diaphragmatic and parietal pleura, confirming metastatic MPM with partial resection performed. This presentation challenges conventional imaging paradigms of MPM, underscoring its diagnostic complexity.
CONCLUSION: MPM should still be considered an important differential diagnosis in young patients presenting with solitary pleural masses and no history of typical asbestos exposure. F-18 FDG PET/CT, while serving as an essential component of initial staging for MPM, has some inherent limitations.

Keywords: Case report; F-18 fluorodeoxyglucose; Malignant pleural mesothelioma; Pleural neoplasms; Positron emission tomography computed tomography

DOI: https://doi.org/10.12998/wjcc.v13.i32.110897

ESMO Open. 2025 Nov 19. pii: S2059-7029(25)01774-0. [Epub ahead of print]10(12): 105905

First-in-human study of a thorium-227-labeled mesothelin-targeting antibody-chelator conjugate (MSLN-TTC), in patients with malignant mesothelioma and other solid tumors.

A Minchom, O Lindén, D G Knapen, R Hassan, F I Lin, K Jalkanen, V Subbiah, A Tafuri, D Ferreira, V Jardine, A Cleton, J Pinkert, F Bladt, H Hennekes, E F Smit.

INTRODUCTION: BAY 2287411 [227Th-anetumab corixetan; mesothelin-targeting antibody-chelator conjugate (MSLN-TTC)] is a targeted alpha therapy consisting of a fully human mesothelin-targeting monoclonal antibody conjugated with a 3,2-hydroxypyridinone (3,2-HOPO) chelator radiolabeled with the alpha particle-emitting radionuclide thorium-227. This phase I study determined the safety, pharmacokinetics, and antitumor activity of MSLN-TTC in mesothelin-expressing mesothelioma and serous ovarian cancer.
METHODS: MSLN-TTC was administered i.v. 1.5, 2.5, or 3.5 MBq of thorium-227 and with a total antibody dose of 10, 30, 50, or 150 mg every 6 weeks to 36 patients included in the intention-to-treat population. Adverse events, tumor response according to RECIST 1.1 and mRECIST criteria, and progression-free survival were determined. Tumor mesothelin expression was assessed retrospectively.
RESULTS: In dose escalation, 35 patients (30 with malignant pleural mesothelioma) received MSLN-TTC across three thorium-227 dose levels and four total antibody doses. No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached due to treatment discontinuations following 45.7% of the patients developing neutralizing antibodies. The most common treatment-emergent adverse events of any grade were fatigue (10/36, 27.8%), decreased lymphocyte count (7/36, 19.4%), nausea (7/36, 19.4%), anemia (6/36, 16.7%), and infusion-related reaction (6/36, 16.7%). The disease control rate was 34.3%, including 12 stable diseases (12/36, 34.3%). No complete or partial responses were observed. The median progression-free survival was 70 days (95% confidence interval 29-161 days).
CONCLUSIONS: MSLN-TTC showed good tolerability, but the maximum tolerated dose could not be determined due to discontinuations after antidrug antibody formation. Stable disease was observed in 12 out of 36 patients.

Keywords: mesothelin; mesothelioma; ovarian cancer; targeted alpha therapy; thorium-227

DOI: https://doi.org/10.1016/j.esmoop.2025.105905