Nature genetics · 2026
Tumor DNA methylation subtypes predict immunotherapy outcomes in pleural mesothelioma patients in the NIBIT-EPI-MESO study.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Calabrò Luana, Caruso Francesca P, Covre Alessia, Noviello Teresa M R, Lofiego Maria F, Tufano Rossella, Ferraro Luigi, Grisolia Piera, De Falco Antonio, Lagano Vincenzo, Sgambelluri Francesco, Sabella Giovanna, Rossi Giulia, Gibilisco Giulia, Marzani Francesco, Bello Emma, Simonetti Elena, D'Alonzo Vincenzo, Caraglia Michele, Coral Sandra, De Angelis Antonina, Cerbone Luigi, Delfanti Sara, Giannarelli Diana, Grosso Federica, Di Giacomo Anna Maria, Milione Massimo, Mortarini Roberta, Anichini Andrea, Ceccarelli Michele, Maio Michele
Аннотация
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.