bims-mesote 2026-05-03 papers

Issue of 2026–05–03
five papers selected by
Laura Mannarino, Humanitas Research

Clin Transl Oncol. 2026 Apr 30.

Clinical and prognostic factors in pleural mesothelioma: insights from a Latin American cohort.

Ricardo Brugés, Carlos Carvajal, Marcela Núñez, Alejandra Navarrete, Rafael Parra-Medina.

BACKGROUND: Pleural mesothelioma (PM) remains a lethal but preventable disease whose burden is shifting toward low- and middle-income countries (LMICs) where asbestos use has persisted or has only recently been banned. This study describes the clinical characteristics, management patterns, and prognostic factors of PM in a contemporary Colombian cohort.
METHODS: We conducted a retrospective cohort study of adults with histologically confirmed pleural mesothelioma diagnosed at a tertiary referral cancer center in Bogotá, Colombia, from January 1, 2011, to December 31, 2023. Overall survival (OS) was defined from the histologic diagnosis date to death from any cause; patients without a recorded death were censored at the last documented oncologic contact. Real-world progression-free survival (PFS) was defined from diagnosis to documented progression (radiologic or clinician-documented) or death, whichever occurred first; patients without progression or death were censored at last contact. Survival was estimated using Kaplan-Meier methods and modeled using Cox proportional hazards regression.
RESULTS: The cohort included 106 patients (mean age, 63.2 years; 73.6% male; 84.9% epithelioid histology). There were 105 deaths (1 OS censor). Median OS was 9.9 months (95% CI, 7.1-14.1), with 12- and 24 month OS of 46.2% and 12.3%. Real-world PFS included 105 events (1 PFS censor). Median PFS was 8.1 months (95% CI, 6.2-9.4), with 12- and 24 month PFS of 30.2% and 6.6%. In multivariable analyses focused on baseline prognostic factors, ECOG performance status 2-3 was associated with shorter OS and PFS.
CONCLUSIONS: In this contemporary Colombian cohort, OS and PFS were short, and baseline functional status was strongly associated with outcomes. Treatment-stratified survival patterns are reported descriptively and should not be interpreted as comparative effectiveness. These data add regional evidence for pleural mesothelioma prognosis in routine practice.

Keywords: Asbestos; Chemotherapy; Colombia; Latin America; Low- and middle-income countries; Mesothelioma; Survival

DOI: https://doi.org/10.1007/s12094-026-04337-1

Lung Cancer. 2026 Apr 27. pii: S0169-5002(26)00488-5. [Epub ahead of print]217 109427

Epidermal growth factor receptor-targeted near-infrared photoimmunotherapy for malignant pleural mesothelioma.

Miyu Kano, Aki Furusawa, Seiichiro Takao, Motofumi Suzuki, Makoto Kano, Hiroshi Yamamoto, Peter L Choyke, Hisataka Kobayashi.

Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer mostly associated with asbestos exposure. Effective treatments are limited, and the prognosis is extremely poor. Therefore, the development of novel therapeutic approaches is highly desirable. Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that specifically kills target cells. It utilizes an antibody-IRDye700DX conjugate that binds target tumor cells. After near-infrared light irradiation of the tumor, rapid and highly selective cell damage results in immunogenic cell death. Anti-epidermal growth factor receptor (EGFR) antibody-IRDye700DX conjugate has already been approved in Japan for the treatment of head and neck cancer with near-infrared laser light activation. EGFR overexpression in MPM makes it a promising candidate for EGFR-targeted NIR-PIT, but its efficacy has not been reported previously. In this study, we investigated the therapeutic effects of NIR-PIT targeting EGFR using an MPM xenograft mouse model. In vitro, three MPM cell lines (NCI-H28, NCI-H226, and MSTO-211H) showed EGFR overexpression on the cell surface. EGFR-targeted NIR-PIT induced cell death in a dose-dependent manner in all MPM cell lines. In vivo, EGFR expression was verified, and anti-EGFR antibody binding was observed in both NCI-H226 and MSTO-211H tumors. After EGFR-targeted NIR-PIT, histological analysis demonstrated cancer cell death which significantly suppressed tumor growth in both tumor models and significantly extended survival in NCI-H226 tumor-bearing mice. Thus, these results suggest that EGFR-targeted NIR-PIT could be a promising treatment approach for MPM.

Keywords: Cancer; Epidermal growth factor receptor; Malignant pleural mesothelioma; Near-infrared photoimmunotherapy; Preclinical model

DOI: https://doi.org/10.1016/j.lungcan.2026.109427

Cancer Drug Resist. 2026 ;9 9

Immunotherapy resistance and strategies in malignant pleural mesothelioma.

Wanyi Xia, Yulong Zhang, Juanzhi Zhao, Xiaoli Tan, Shaolong Ju, Wei Zou, Chaoqun Chen, Chunwei Li, Yanghua Xu, Yingming Peng, Shengqiao Li.

Malignant pleural mesothelioma (MPM) remains one of the most aggressive thoracic malignancies, characterized by profound resistance to conventional modalities such as surgery, chemotherapy, and radiotherapy, resulting in persistently poor survival outcomes. The advent of immune checkpoint inhibitors (ICIs) has fundamentally reshaped the therapeutic landscape of MPM. Notably, dual programmed cell death protein 1 (PD-1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade has demonstrated superior efficacy over monotherapy in multiple phase I/II trials and has been established as a novel first-line standard of care. Nevertheless, the high incidence of resistance continues to pose a major clinical challenge. This therapeutic bottleneck is largely attributed to the unique biology of MPM, including a profoundly immunosuppressive tumor microenvironment, aberrantly activated signaling pathways, and complex metabolic reprogramming, which together form a multilayered defense network against immune attack. In response to this intricate resistance architecture, recent research efforts have increasingly focused on the development of precision combination strategies. By rationally integrating ICIs with anti-angiogenic agents, chemotherapy, metabolic modulators, and next-generation cellular immunotherapies [e.g., chimeric antigen receptor T cells (CAR-T), chimeric antigen receptor-natural killer (CAR-NK)], these approaches aim to dismantle immune evasion barriers and reinvigorate antitumor immunity. Concurrently, the discovery of novel biomarkers and their integration with multi-omics data are enabling more precise patient stratification, signaling the advent of an era of personalized immunotherapy for MPM. This review provides a systematic synthesis of the latest clinical advances and fundamental breakthroughs in MPM immunotherapy, with a particular focus on dissecting the multifactorial mechanisms underlying therapeutic resistance. Its core contribution lies in constructing a forward-looking framework for next-generation treatment strategies. It critically evaluates the translational potential of emerging approaches, including arginine deprivation therapy for argininosuccinate synthase 1 (ASS1)-deficient tumors, CAR-T cells, T-cell receptor fusion constructs, and oncolytic virotherapy. By integrating these innovative modalities with biomarker-guided patient selection, this review delineates a roadmap for transitioning MPM management from empirical therapy toward precision immuno-oncology, with the ultimate goal of achieving durable disease control in this challenging malignancy.

Keywords: Malignant pleural mesothelioma; immunotherapy; resistance to immune checkpoint inhibitors; tumor microenvironment

DOI: https://doi.org/10.20517/cdr.2025.215

Nat Genet. 2026 Apr 27.

Tumor DNA methylation subtypes predict immunotherapy outcomes in pleural mesothelioma patients in the NIBIT-EPI-MESO study.

Pleural mesothelioma (PM) has a poor prognosis and standard therapy with immune checkpoint inhibitors (ICIs) CTLA-4 and PD-1 is still clinically unsatisfying. No predictive biomarkers of ICI efficacy in PM are available yet. In the retrospective multicenter NIBIT-EPI-MESO study, multi-omics analysis of pre-ICI therapy tumor lesions from 91 patients with PM treated in earlier clinical trials or in daily practice identified four PM subsets with progressively increasing global DNA methylation profiles-demethylated, LOW, intermediate and CpG island methylator phenotype (CIMP). These methylation subsets predicted response and survival to ICI therapy. The LOW subset was enriched in responder patients, who had the longest median overall survival and the highest 3-year overall survival rate, and showed a T cell- and B cell-rich immune microenvironment. Conversely, the CIMP subtype was enriched in nonresponder patients with the shortest median overall survival and overall survival, along with a depleted immune microenvironment. A methylation-based probabilistic decision-making classification tool to predict the outcome of ICI treatment in patients with PM was developed.

DOI: https://doi.org/10.1038/s41588-026-02580-4

Br J Cancer. 2026 Apr 27.

Multiplexed single-cell and spatial profiling reveal B cells and tertiary lymphoid structures as prognostic indicators in pleural mesothelioma.

Angelica Rigutto, Nicolás G Núñez, Jenny C Kienzler, Isabelle Opitz, Mayura Meerang, Martina Haberecker, Nadine Fournier, Joao Lourenço, Raphael Gottardo, Karina Silina, Anurag Gupta, Burkhard Becher, Alessandra Curioni-Fontecedro.

BACKGROUND: Pleural mesothelioma (PM) is an orphan disease with poor prognosis. While T cell dynamics in the tumor microenvironment (TME) have been extensively studied, the role of B cells remains poorly characterized. Tumor-infiltrating B cells, particularly when organized into tertiary lymphoid structures (TLS), have been associated with improved outcomes of patients with cancer.
METHODS: In this study, high-dimensional flow cytometry (HDCyto) and high-plex imaging were applied to analyze fresh-frozen and formalin-fixed paraffin-embedded (FFPE) PM tumor samples, enabling a comprehensive immune profiling of the TME.
RESULTS: We identified 15 distinct immune cell subsets and stratified tumors into three subgroups with significantly different survival outcomes. Longer survival correlated with increased T and B cell infiltration, with B cells and CD4+ T cells forming TLS in specific cases.
CONCLUSIONS: These findings underscore the heterogeneity of PM tumors and highlight the critical role of B cells and TLS in shaping anti-tumor immunity and influencing patient prognosis.

DOI: https://doi.org/10.1038/s41416-026-03421-1