179 Characterisation of tumour-directed B cell responses in glioblastoma through single-cell transcriptomics and serological profiling

Abstract

Glioblastoma (GBM) is the most common and aggressive primary brain tumour in adults, with a median survival of approximately 15 months despite multimodal treatment. The GBM tumour microenvironment is recognised as profoundly immunosuppressive, yet the role of B cell-mediated humoral immunity remains largely unexplored. This study aims to characterise B cell responses in GBM through integrated computational and serological approaches to identify tumour-directed antibody responses. We performed a meta-analysis of single-cell RNA sequencing datasets from GBM to characterise tumour-infiltrating B cell programmes, contextualised against a pan-cancer B cell atlas. Pathway enrichment analysis compared B cell receptor signalling activity across cancer types. Serological profiling was then performed on plasma from a local cohort of 25 individuals with GBM, assessing antibody binding against patient-derived glioma stem cell (GSC) lines and control cell lines. Meta-analysis revealed a distinct B cell signature in GBM, with significant enrichment of B cell receptor signalling pathways compared to other cancers. Phenotypic characterisation identified germinal centre-like B cells, indicative of active, antigen-driven humoral responses. Indeed, subsequent serological profiling demonstrated that 20% of individuals (n = 5/25) harboured circulating antibodies with detectable binding across all three GSC lines, with no reactivity against controls, suggesting tumour-specific humoral responses.