Tumor-infiltrating and circulating B cells mediate local and systemic immunomodulatory mechanisms in Glioblastoma.

backgroundGlioblastoma (GBM) demonstrates extensive immunomodulatory mechanisms that challenge effective therapeutic interventions. These phenomena extend well beyond the tumor microenvironment (TME) and are reflected in the circulating immunophenotype. B lymphocytes (B cells) have received limited attention in GBM studies despite their emerging importance in mediating both local and systemic immune responses. Recent findings highlight the complex regulatory interactions between B cells and other immune cell populations, including tumor-infiltrating macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and other infiltrating lymphocytes (TILs). B cells are believed to hinder the efficacy of modern immunotherapy strategies focusing on T cells.

methodsThis is a focused review of available evidence regarding B cells in GBM through January 2025.

resultsPeripheral blood reflects a systemically dampened immune response, with sustained lymphopenia, increased plasma cells, and dysfunctional memory B cells. The tumor immune landscape is enriched in cells of B-lineage. Subsets of poorly characterized B regulatory cells (Bregs) populate the TME, developing their phenotype due to their proximity to MDSCs, TAMs, and tumoral cells. The Bregs inhibit CD8

conclusionUnderstanding the role of B cells, how they are recruited, and their differentiation shifted towards an immunomodulatory role could inform better therapeutic strategies and unleash their full antitumoral potential in GBM.