bims-mesote 2026-07-05 papers

Thorac Cancer. 2026 Jul;17(13): e70343

BAP1 Loss Might Be a Predictive Biomarker for Immunotherapy Response in Pleural Mesothelioma.

Reina Imase, Rie Sakakibara, Susumu Kirimura, Hironori Ishibashi, Kenichi Okubo, Yasunari Miyazaki.

INTRODUCTION: Reliable predictive biomarkers for immune checkpoint inhibitors (ICIs) in pleural mesothelioma (PM) are lacking. Loss of BRCA1-associated protein 1 (BAP1) is a frequent molecular alteration in PM and may influence the tumor immune microenvironment. We evaluated whether BAP1 loss is associated with clinical outcomes following immunotherapy.
METHODS: We retrospectively analyzed 14 patients with PM who were treated with ICIs between April 2014 and May 2024. BAP1 status was assessed by immunohistochemical staining of resected tumor specimens. Patients were categorized into BAP1-loss and BAP1-positive groups. Progression-free survival (PFS), overall survival (OS), response rate (RR), and disease control rate (DCR) were compared.
RESULTS: BAP1 loss was observed in nine patients (64%). Median PFS was significantly longer in the BAP1-loss group compared with the BAP1-positive group (5.3 vs. 2.1 months; log-rank p = 0.03). Median OS was also prolonged in the BAP1-loss group (8.6 vs. 2.1 months; log-rank p = 0.03). RR and DCR were numerically higher among patients with BAP1 loss.
CONCLUSION: BAP1 loss was associated with improved clinical outcomes following immunotherapy in PM. These findings support that a molecular profile that includes BAP1 deletion may serve as a biomarker for predicting response to immunotherapy in PM.

Keywords: BAP1; immune checkpoint inhibitor; immunohistochemistry; immunotherapy; pleural mesothelioma

DOI: https://doi.org/10.1111/1759-7714.70343

Cureus. 2026 Jun;18(6): e110026

Long-Term Disease Control With Second-Line Nivolumab Monotherapy in Malignant Pleural Mesothelioma: A Case Report.

Shohei Otsuka, Kei Hiraoka, Nozomu Iwashiro.

Nivolumab is recommended as second-line therapy for malignant pleural mesothelioma (MPM); however, durable responses remain uncommon. In addition, combination immune checkpoint inhibitors are frequently limited by immune-related adverse events. A 72-year-old man with epithelioid MPM underwent extrapleural pneumonectomy followed by adjuvant chemotherapy with cisplatin and pemetrexed. After recurrence, additional platinum-based chemotherapy was administered, followed by disease progression. Nivolumab monotherapy was then initiated as second-line therapy, resulting in a sustained radiological response. The patient has maintained progression-free survival for 24 months without severe immune-related adverse events, allowing long-term treatment continuation. This case highlights that nivolumab monotherapy may achieve durable disease control with a favorable safety profile in selected patients with MPM.

Keywords: immune-related adverse events; malignant pleural mesothelioma; nivolumab; progression-free survival; second-line therapy

DOI: https://doi.org/10.7759/cureus.110026

Clin Lung Cancer. 2026 Jul;pii: S1525-7304(26)00081-1. [Epub ahead of print]27(6): 68-74

Outcomes of Platinum Plus Pemetrexed and Treatment Patterns Following First-Line Nivolumab and Ipilimumab in Pleural Mesothelioma: Real-World Results From the German MesoNet Study.

BACKGROUND: There is currently no approval for second-line treatment in pleural mesothelioma (PM). Since the approval of nivolumab/ipilimumab, most guidelines recommend platinum/pemetrexed as subsequent treatment. However, the data supporting this sequence are primarily based on efficacy observed in the first-line setting, while evidence regarding the use of platinum/pemetrexed following first-line nivolumab/ipilimumab remains scarce.
METHODS: In this retrospective, multicenter study, 57 patients with PM who received second-line therapy were included from the MesoNet cohort, comprising 12 participating cancer centers across Germany. The primary objective was to evaluate outcomes in patients who received second-line platinum/pemetrexed following nivolumab/ipilimumab. The secondary objective was to explore subsequent treatment patterns.
RESULTS: Among 135 patients treated with first-line nivolumab/ipilimumab, 57 (42%) received second-line treatment, of whom 41 (72%) received platinum/pemetrexed. The median OS (overall survival) and median PFS (progression-free survival) with second-line platinum/pemetrexed were 11.5 months (95% confidence intervals [CI] 8.6-13.8) and 5.8 months (95% CI 4.1-7), respectively. The disease control rate was 72%, with partial response observed in 28% of patients. Subtype analysis revealed a trend toward better median OS in nonepithelioid versus epithelioid histology (13 months vs. 9.5 months). Only 22 patients (16% of the first-line cohort) received third-line treatment, indicating substantial treatment attrition.
CONCLUSION: In this real-world study, second-line platinum/pemetrexed following first-line nivolumab/ipilimumab demonstrated meaningful clinical activity with an mOS of 11.5 months from the initiation of second-line treatment. These findings support platinum/pemetrexed as an effective second-line option in this setting. However, the high treatment attrition rate emphasizes the importance of careful patient selection and early initiation of second-line therapy.

Keywords: Chemotherapy; Immunotherapy; Pemetrexed; Platinum; Second-line

DOI: https://doi.org/10.1016/j.cllc.2026.06.001

Lung Cancer. 2026 Jun 28. pii: S0169-5002(26)00573-8. [Epub ahead of print]218 109512

Genome-wide copy number analysis identifies AKT as a novel therapeutic target in pleural mesothelioma.

Claudia Kalla, Dina Mönch, Sophia Steinlein, Alessandro Pastore, Heike Horn, Roger Falkenstern-Ge, Julia Schüler, German Ott, Gerhard Preissler.

PURPOSE: Targeting aberrantly activated kinases in pleural mesothelioma (PM) is a promising therapeutic strategy. To identify potential candidates, we characterized recurrent chromosomal gains in PM and subsequently evaluated the specific inhibition of kinases that were activated by amplification and/or overexpression.
METHODS: 42 primary PM were screened for chromosomal alterations using OncoScan technology and AKT expression was assessed using immunohistochemistry. The impact of Ipatasertib (pan-AKT inhibitor) and Sapanisertib (mTOR inhibitor) on cell survival, apoptosis induction, AKT/mTOR signaling, glycolysis was investigated in cell lines and primary cells. Preclinical anti-tumor efficacy was further assessed in a PDX model selected for AKT and mTOR expression.
RESULTS: OncoScan profiling identified eleven regions of significant chromosomal gains. Among them, 14q32.33 and 19q13.2 gains affected AKT1 and AKT2, members of the AKT serine/threonine protein kinase family. AKT1 protein was expressed in 66 % (60/91), AKT2 in 80 % (73/91) and AKT3 in 94 % (86/91) PM. 57 % PM co-expressed AKT1/AKT2/AKT3. Treatment with Ipatasertib impaired cell viability in PM cell lines and induced apoptosis. Combined treatment with Ipatasertib and Sapanisertib had a synergistic cytotoxic effect in all three cell lines and primary cells from two PM patients, even in Cisplatin-resistant cells. We also noted an improved response to the combination in a PDX model. Mechanistically, the combined treatment acted synergistically to inactivate AKT/mTOR downstream signaling, suppress glycolysis, and trigger ATP depletion.
CONCLUSIONS: Our study demonstrates recurrent activation of AKT kinases by copy number gains and upregulated expression in PM. Pharmacological AKT and mTOR inhibition is a promising therapeutic alternative for mesothelioma.

Keywords: AKT; Ipatasertib; OncoScan CNV analysis; Pleural mesothelioma; Sapanisertib

DOI: https://doi.org/10.1016/j.lungcan.2026.109512

In Vivo. 2026 Jul-Aug;40(4):40(4): 2204-2224

Impact of CD73/CD155 Expression on Survival in Resected Epithelial Pleural Mesothelioma: A Retrospective Single-center Study.

Yusuke Nabe, Yasuhiro Fujita, Teppei Hashimoto, Kanji Tanaka, Takehiko Manabe, Katsuma Yoshimatsu, Yukiko Nemoto, Natsumasa Nishizawa, Rintaro Oyama, Yohei Honda, Masataka Mori, Hiroki Matsumiya, Masatoshi Kanayama, Akihiro Taira, Masaru Takenaka, Koji Kuroda, Shohei Shimajiri, Fumihiro Tanaka.

BACKGROUND/AIM: While CD73 and CD155 are implicated in immune evasion and tumor progression, their roles in pleural mesothelioma (PM) remain unclear. Therefore, we investigated the association between CD73 and CD155 expression in resected epithelial PM specimens and explored their impact on 5-year progression-free survival (PFS) and 5-year overall survival (OS).
PATIENTS AND METHODS: This single-center retrospective study enrolled 43 patients with epithelial PM who underwent curative-intent surgery, with/without chemotherapy and immune checkpoint inhibitor (ICI) treatment, between January 2013 and December 2020. HALO-AI pathology software was used to quantify CD73 and CD155 expression following immunohistochemical staining. Cutoff values for CD73/CD155 positivity were determined using receiver operating characteristic curves. Patients were categorized into CD73+/CD155+ and non-CD73+/CD155+ groups, and survival outcomes were analyzed using Kaplan-Meier curves and Cox proportional hazards regression.
RESULTS: Among 35 cases, patients with CD73+/CD155+ tumors exhibited significantly improved 5-year PFS compared with those with non-CD73+/CD155+ tumors (64.8% vs. 10.8%, p=0.017); however, OS differences were not significant (p=0.376). Among CD73+/CD155+ cases, postoperative pleurodesis with OK432 was associated with improved PFS (83.3% vs. 33.3%, p=0.03). Among non-CD73+/CD155+ cases, postoperative chemotherapy significantly improved PFS (p<0.001). Univariate analysis identified non-CD73+/CD155+ expression as an independent predictor of disease progression [hazard ratio (HR)=0.2546, p=0.02933]. Among recurrent cases, patients treated with ICIs exhibited significantly improved OS (p=0.001), highlighting the potential of immunotherapy.
CONCLUSION: CD155 may serve as a poor prognostic factor in mesothelioma and represents the first immunohistochemical evaluation of this marker. Although CD73 and CD155 co-expression were initially predicted to indicate poor prognosis, findings were unexpected, likely due to inability to establish an optimal cutoff value given variations in patient demographics, disease stage, and treatment approaches.

Keywords: CD155 antigen; CD73 antigen; adjuvant; chemotherapy; disease progression; immunotherapy; pleural mesothelioma; pleurodesis; prognostic biomarkers; survival analysis

DOI: https://doi.org/10.21873/invivo.14373

J Pers Med. 2026 Jun 30. pii: 356. [Epub ahead of print]16(7):

RETRACTED: Zito Marino et al. AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma. J. Pers. Med. 2022, 12, 1993.

Federica Zito Marino, Carminia Maria Della Corte, Vincenza Ciaramella, Stefania Erra, Andrea Ronchi, Alfonso Fiorelli, Giovanni Vicidomini, Mario Santini, Giosuè Scognamiglio, Floriana Morgillo, Fortunato Ciardiello, Renato Franco, Marina Accardo.

The journal retracts the article titled "AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma" [...].

DOI: https://doi.org/10.3390/jpm16070356

BMJ Open Respir Res. 2026 Jul 01. pii: e004045. [Epub ahead of print]13(1):

Protocol for Mesothelioma Observational study of Risk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy (Meso-ORIGINS).

INTRODUCTION: Pleural mesothelioma (PM) is often presaged by benign asbestos-associated pleural inflammation (AAPI), offering a unique window of opportunity for translational research. The PREDICT-Meso International Accelerator Network is leveraging this natural history to perform target identification and develop novel therapies for early-stage or pre-invasive disease. This requires assembly of a unique bioresource of longitudinal human tissue samples spanning the terminal stages of PM evolution, development of preclinical models for drug screening and reliable tools for risk prediction in patients presenting with AAPI.
METHODS AND ANALYSIS: Mesothelioma Observational study of Risk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy (Meso-ORIGINS) is a prospective, multicentre observational study, comprising two arms (A and B), with a nested MRI substudy in arm A. Arm A will recruit 300 AAPI patients and perform 6-monthly surveillance for 2 years. Suspicion of PM evolution will prompt repeat biopsy and banking, delivering a primary objective of ≥38 longitudinal AAPI-PM tissue pairs. This target reflects a projected PM evolution rate of 14% (95% CI 10.5 to 19.2) derived from a prior multicentre feasibility trial. Multiomic risk profiling will be performed in arm A, using blood proteomics, exhaled breath metabolomics and perfusion MRI. Arm B will recruit 300 patients with suspected PM, permitting collection of multiregion pleural biopsies in patients spanning AAPI and PM timepoints for evaluation of anatomical heterogeneity. Where possible, patients in arm B diagnosed with AAPI will be recruited to arm A for 2-year surveillance +/- repeat biopsy in subsequent PM evolution cases. Pleural fluid will be collected in arm B for cell-line generation and diagnostic biomarker evaluation. Exhaled breath will be collected in arm B for diagnostic biomarker evaluation.
ETHICS AND DISSEMINATION: The study has ethical approval (REC Ref 21/WS/0120). Results will be disseminated via peer-reviewed journals and national/international scientific conferences. Tissues, data and derived omics will be shared via the PREDICT-Meso Research Tissue Bank (REC Ref 21/WS/0011).
TRIAL REGISTRATION NUMBER: ISRCTN22929761.

Keywords: Asbestos Induced Lung Disease; Mesothelioma; Pleural Disease

DOI: https://doi.org/10.1136/bmjresp-2025-004045