bims-mesote Biomed News
on Mesothelioma
Issue of 2026–02–22
nine papers selected by
Laura Mannarino, Humanitas Research



  1. Thorax. 2026 Feb 17. pii: thorax-2025-223284. [Epub ahead of print]
       BACKGROUND: Pleural mesothelioma (PM) is a rare tumour, usually associated with previous asbestos exposure. Standard frontline, pemetrexed/platinum-based chemotherapy has been challenged since 2020 by dual immunotherapy, that is, anti-programmed cell death-1 (anti-PD-1) + anti-cytotoxic T lymphocyte-associated antigen-4 immune checkpoint inhibitors and recently by combination of chemotherapy + anti-PD-1. However, PM prognosis remains globally poor, without validated curative treatment to date.
    METHODS: We reviewed alternative pre-clinical models and clinical data for the evaluation of new treatments and strategies to optimize response to immunotherapies in pleural mesothelioma.
    RESULTS: Various innovative immunotherapies alone or combined with standard treatments and/or targeted therapies are currently assessed by clinical trials. The evaluation of these new strategies deserves relevant preclinical models, requiring the use of human models in addition to or even instead of mouse models. These models recapitulate, at least partially, heterogeneity of the tumours and offer new perspectives for the development and evaluation of immunotherapies. However, like all models, they exhibit advantages and disadvantages needing to be identified in order to use them to answer a well-defined biological question.
    CONCLUSIONS: Along with ongoing trials testing innovative immunotherapies and strategies in pleural mesothelioma, original pre-clinical models are required to optimize these strategies and discover new ones for our patients.
    Keywords:  Asbestos Induced Lung Disease; Lymphocyte Biology; Mesothelioma; Pleural Disease
    DOI:  https://doi.org/10.1136/thorax-2025-223284
  2. Cytopathology. 2026 Feb 20.
       BACKGROUND: To understand the efficacy of pleural effusion cytology in the diagnosis of malignant mesothelioma, we conducted this retrospective study to review the pleural fluid cytologies of patients diagnosed on concurrent/recent pleural biopsy histology. The clinicopathologic features and common cytomorphology were analysed.
    METHODS: Patients who underwent pleural biopsy/stripping and had concurrent/recent pleural fluid cytology between May 2004 and December 2023 at Rush University Medical Center in Chicago were included in our study. All pleural fluid specimens initially collected and preserved in CytoLyt Solution (Hologic, Marlborough, MA) were processed into ThinPrep slides using a standardised laboratory protocol. The cytology diagnoses were made based on a combination of Papanicolaou stained ThinPrep slides, H&E stained cell block and immunohistochemistry on cell block.
    RESULTS: A total of 26 patients with malignant pleural mesothelioma diagnosed on pleural biopsy/stripping who also had concurrent/recent pleural fluid cytology were identified. About 53.8% (14/26) of pleural fluid cytologies were negative. The most common initial interpretations for the negative findings were reactive mesothelial cells (8/14), mixed inflammatory cells (12/14) and macrophages (2/14). Indeterminate pleural fluid cytologies accounted for 19.2% (5/26) of specimens in our study, with 11.5% being atypical and 7.7% suspicious for malignancy. Malignant pleural fluid cytologies accounted for 26.9% (7/26) of our cases. Surgical pathology specimens included 22 pleural biopsies and 4 pleural strippings, all of which confirmed malignant pleural mesothelioma. The subtypes of malignant pleural mesothelioma included 18 epithelioid, 4 sarcomatoid and 4 biphasic mesothelioma subtypes. The sensitivity of pleural fluid cytology alone in our study was low, at 26.9%. However, when including the 'Atypical cells present' and 'Suspicious for malignancy' categories as abnormal cytology, the sensitivity increased to 46.2%.
    CONCLUSION: In conclusion, we report that a diagnosis of mesothelioma can be made from pleural fluid cytology samples in a subset of patients, albeit with a relatively low sensitivity (26.9%).
    Keywords:  malignant mesothelioma; mesothelioma; mesothelioma in situ; pleural biopsy; pleural fluid cytology
    DOI:  https://doi.org/10.1111/cyt.70058
  3. Surg Case Rep. 2026 ;pii: 25-0774. [Epub ahead of print]12(1):
       INTRODUCTION: Gastrointestinal metastasis from malignant pleural mesothelioma (MPM) is exceedingly rare and lacks a standardized diagnostic work-up.
    CASE PRESENTATION: An 87-year-old man with asbestos exposure and a 5-year history of left-sided MPM, radiographically stable on long-term nivolumab therapy, presented with melena and anemia. Contrast-enhanced CT revealed a circumferential jejunal lesion near the duodenojejunal flexure with enlarged mesenteric nodes. Double-balloon enteroscopy confirmed a 40-mm obstructive tumor, but biopsies were non-diagnostic. Partial jejunectomy with targeted mesenteric lymph-node dissection was performed. Histology with a mesothelioma-oriented immunohistochemical panel-negative for CEA and BerEP4 and positive for broad-spectrum cytokeratins-supported a diagnosis of metastatic MPM; nodal metastases were present. Given his age, no further systemic therapy was administered; the patient died 20 months postoperatively from progression of MPM.
    CONCLUSIONS: In MPM receiving immune-checkpoint inhibitor therapy, unexplained gastrointestinal bleeding should prompt comprehensive gastrointestinal evaluation, including small-bowel assessment. Surgery can secure symptom relief and a definitive diagnosis.
    Keywords:  immune-checkpoint inhibitors; jejunal metastasis; malignant pleural mesothelioma; small-bowel metastasis
    DOI:  https://doi.org/10.70352/scrj.cr.25-0774
  4. Ther Adv Med Oncol. 2026 ;18 17588359261420028
      Mesothelioma is a rare cancer that carries a poor prognosis. This malignancy has had few therapeutic advances prior to the introduction of immune checkpoint inhibitors. Immunotherapy is now a cornerstone of first-line treatment for pleural mesothelioma and has been shown to provide clinical benefit for relapsed or refractory patients treated with prior chemotherapy. This review article will discuss key immunotherapy trials in the scientific literature, along with challenges in the application of this therapy. We will also discuss future areas of immunotherapy research in the treatment of mesothelioma.
    Keywords:  checkpoint inhibitors; immunotherapy; lung cancer; medical oncology; novel therapies
    DOI:  https://doi.org/10.1177/17588359261420028
  5. J Thorac Oncol. 2026 Feb 20. pii: S1556-0864(26)00003-1. [Epub ahead of print] 103551
      Despite recent advances in the treatment of pleural mesothelioma, it remains a challenging and heterogeneous disease, with limited options for patients. Survival rates have only marginally improved in the past years, highlighting the need for a better biological understanding of the disease for the translation into clinical practice. Although recent years have seen substantial progress in genomics and molecular pathology, much of the existing literature has focused on morphology-correlated changes, with molecular, immunohistochemical, clinical, and blood biomarkers largely studied in a correlative framework. Despite these efforts, TNM classification remains the most powerful predictor of survival and one of the most important parameters to guide therapy in clinical practice. However, emerging evidence reveals that histology alone fails to capture the full heterogeneity of the disease, leading to suboptimal diagnostic, prognostic, and therapeutic approaches. This review summarizes recent major molecular findings relating not only to histology but also ploidy, tumor microenvironment, and methylation-which together offer a more comprehensive understanding of interpatient heterogeneity. In light of these results, we discuss the potential for a new morpho-molecular classification based on these molecular findings to overcome the current clinical challenges. Future directions for the field are also proposed, including the potential for emerging technologies such as single-cell, spatial omics, and artificial intelligence to fill in the gaps of bulk studies and unveil clinically relevant information about pleural mesothelioma tumor heterogeneity.
    Keywords:  Genomics; Morpho-molecular classification; Pleural mesothelioma; Single-cell sequencing; Tumor heterogeneity
    DOI:  https://doi.org/10.1016/j.jtho.2026.01.003
  6. Int J Biol Markers. 2026 Feb 19. 3936155261421213
      PurposeThis study aimed to investigate KRAB-associated protein 1 (KAP1) expression in pleural mesothelioma (PM) and its impact on the biological behavior of the human pleural mesothelioma cell line MSTO-211H, providing a specific biomarker for the early clinical diagnosis of PM.Patients and methodsKAP1 expression levels in PM tissues were detected using immunohistochemistry. Lentivirus infection was used to construct MSTO-211H mesothelioma cell lines with stable KAP1 overexpression or knockdown, and the efficiency of KAP1 overexpression or knockdown was detected using qRT-PCR(quantitative Reverse Transcription PCR) and Western blotting. The effects of KAP1 overexpression and knockdown on MSTO-211H mesothelioma cell proliferation, migration, and invasion were detected using cell counting kit-8, plate colony formation, cell scratch, and transwell invasion assays, respectively. The effects of KAP1 overexpression and knockdown on the cell cycle, related cyclins, and apoptosis were detected using flow cytometry. Gene enrichment and correlation analysis of mesothelioma were performed using bioinformatics analysis.ResultsKAP1 was significantly overexpressed in PM tissues compared with normal pleural tissues (P < 0.05). Compared to the control group, KAP1 overexpression in mesothelioma MSTO-211H cells significantly enhanced proliferation, migration, and invasion (P < 0.05), without causing cell cycle arrest, and significantly increased the mRNA and protein levels of cyclin D1 and cyclin E (P < 0.05), whereas the apoptosis rate did not significantly change (P > 0.05). Conversely, KAP1 knockdown in mesothelioma MSTO-211H cells significantly inhibited their proliferation, migration, and invasion abilities (P < 0.05), induced G0/G1 phase arrest in the cell cycle, and significantly increased the apoptosis rate (P < 0.05). Spearman correlation analysis revealed significant positive associations between KAP1 mRNA expression and TP53 and SHOX2. Conversely, KAP1 expression was significantly negatively correlated with MTAP and MSLN. GSEA reveals KAP1-associated enrichment of DNA repair, cell cycle, and proteostasis pathways in TCGA-MESO.ConclusionKAP1 is highly expressed in PM and functions as an oncogene-like regulator, enhancing tumor cell growth and aggressiveness.Clinical trial registration2023-28.
    Keywords:  KAP1; apoptosis; cell cycle; pleural mesothelioma; proliferation
    DOI:  https://doi.org/10.1177/03936155261421213
  7. Clin Physiol Funct Imaging. 2026 Mar;46(2): e70053
      Reliable tools for objective response assessment are essential in pleural mesothelioma treated with immunotherapy. We report on a 75-year-old man with sarcomatoid pleural mesothelioma who received a reduced nivolumab dose after developing a hypersensitivity reaction during the first infusion. CT, [18F]FDG PET/CT and [68Ga]Ga-Fibroblast activation protein inhibitor-46 (FAPI) PET/CT were performed before and after treatment. Despite the reduced dose, the patient experienced clear clinical benefit, and follow-up imaging demonstrated substantial morphological and metabolic improvement across all imaging modalities. This case offers an unique opportunity to directly compare response assessment across three complimentary imaging modalities.
    Keywords:  CT; FAPI; FDG; PET; pleural mesothelioma; response assessment
    DOI:  https://doi.org/10.1111/cpf.70053
  8. Curr Oncol Rep. 2026 Feb 18. 28(1): 16
      
    Keywords:  Chemotherapy; Drug delivery; Immunotherapy; Pleural mesothelioma; Targeted therapy
    DOI:  https://doi.org/10.1007/s11912-026-01755-w