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Spatial immune profiling defines a subset of human gliomas with functional tertiary lymphoid structures

ABSTRACT: Adult-type diffuse gliomas, the most common primary brain tumors, remain a clinical challenge in oncology with limited treatment options, restricted anti-tumor immune response and dismal patient prognosis. Despite their immunosuppressive microenvironment, the formation of lymphoid aggregates containing adaptive immune cells has been reported in gliomas. However, the cellular composition, immunological function, and relevance of lymphoid aggregates for adaptive anti-glioma immunity is not well understood. Therefore, we performed a comprehensive, unbiased analysis of lymphoid aggregation in 642 adult-type diffuse gliomas using a multi-modal approach; combining DNA methylation, RNA sequencing with spatial transcriptome and proteome profiling. Overall, B cell aggregates and tertiary lymphoid structures (TLS) were observed in 15% of tumors and associated with an improved overall survival. Gliomas containing TLS displayed a remodeled perivascular space, characterized by transcriptional upregulation and spatial redistribution of collagens associated with barrier functions. Spatial transcriptome and proteome profiling revealed heterogeneous B:T cell interactions that were associated with elevated CD8 T-cell numbers and differences in IgA and IgG plasma-cell forming capacity, suggestive of dynamic adaptive immune responses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE302502 | GEO | 2025/09/01

REPOSITORIES: GEO

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