Multiomics Analysis of Malignant Pleural Mesothelioma Reveals the Immunological Microenvironment Associated with MTAP Loss and Immunotherapy Outcomes.

MTAP loss in unresectable malignant pleural mesothelioma is linked to higher ICI response rates and immune features, including increased CD8+ T-cell infiltration and T-cell receptor diversity in the C-CAT cohort.

• Why it matters: Biomarkers that predict immune checkpoint inhibitor efficacy in malignant pleural mesothelioma are still undefined, limiting patient selection for nivolumab plus ipilimumab.
• What they did: The study analyzed two independent MPM cohorts using whole-genome sequencing and RNA sequencing, plus immune cell composition and T-cell receptor repertoire profiling, with key findings validated in the nationwide C-CAT cohort.
• The result: ICI responders had higher T-cell receptor diversity, increased CD8+ T-cell infiltration, and M1 macrophage enrichment versus non-responders, and MTAP loss was associated with a higher ICI response rate in C-CAT, supporting MTAP loss as a candidate biomarker.

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