Immune landscape-driven subtyping reveals distinct microenvironment and prognostic profiles in thymic epithelial...

Thymic epithelial tumors (TETs) exhibit marked heterogeneity that challenges clinical management and prognostic evaluation. By consensus clustering of immune-related gene expression from public datasets and an in-house validation cohort, we identified two immune subtypes: a lymphocyte-rich subtype (LRS, n = 86) characterized by strong T-cell activity and favorable prognosis, and a myeloid/stromal-rich subtype (MSRS, n = 33) defined by immunosuppressive features, stemness, oncogenic alterations, and poorer outcomes. An APC gene-based classification panel demonstrated robust performance in distinguishing these subtypes, as confirmed by ROC curve analysis and validated in the Ruijin cohort using FFPE-RNA sequencing and multiplex immunofluorescence. Single-cell transcriptomics further delineated subtype-specific tumor microenvironment features and revealed that MSRS tumors suppressed CD8+ T-cell function through MIF-mediated mechanisms. Collectively, these findings establish a clinically relevant immune classification of TETs that integrates molecular, immunological, and clinical features, providing insights into tumor heterogeneity and supporting the development of personalized therapeutic strategies.