TMIC-39. SPATIAL MULTIOMICS PROFILING REVEALS HETEROGENEITY OF B:T CELL INTERACTIONS AND PLASMA CELL FORMATION IN TERTIARY LYMPHOID STRUCTURES IN HUMAN GLIOMAS

Abstract Adult-type diffuse gliomas, the most common primary brain tumours, remain a clinical challenge in oncology with limited treatment options, restricted anti-tumour immune response and a dismal patient prognosis. Despite their immunosuppressive microenvironment, the formation of lymphoid aggregates containing adaptive immune cells has been reported in gliomas. However, the cellular compositions, immunological function, and relevance of lymphoid aggregates for adaptive anti-tumour 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 and RNA sequencing with spatial transcriptome and proteome profiling. Overall, B cell aggregates and tertiary lymphoid structures (TLS) were observed in 15% of tumours, with the highest prevalence in primary glioma localised to the temporoparietal lobe. The presence of TLS was associated with an improved overall survival. Gliomas containing TLS displayed a remodelled perivascular space, characterised by transcriptional upregulation and spatial redistribution of collagens associated with barrier functions. Spatial transcriptome and proteome profiling revealed heterogenous 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 response.