De Domenico Pierfrancesco, Gagliardi Filippo, Roncelli Francesca, Snider Silvia, Mortini Pietro
Department of Neurosurgery and Gamma Knife Radiosurgery, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Via Olgettina 60, 20132, Milan, Italy.
J Neurooncol. 2025 May;172(3):527-548. doi: 10.1007/s11060-025-04989-z. Epub 2025 Mar 13.
Glioblastoma (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.
This is a focused review of available evidence regarding B cells in GBM through January 2025.
Peripheral 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 T activity and may have potential prognostic significance.
Understanding 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.
胶质母细胞瘤（GBM）展现出广泛的免疫调节机制，对有效的治疗干预构成挑战。这些现象远远超出肿瘤微环境（TME）的范畴，并反映在循环免疫表型中。尽管B淋巴细胞（B细胞）在介导局部和全身免疫反应中日益重要，但在GBM研究中受到的关注有限。最近的研究结果突出了B细胞与其他免疫细胞群体之间复杂的调节相互作用，包括肿瘤浸润巨噬细胞（TAM）、髓源性抑制细胞（MDSC）和其他浸润淋巴细胞（TIL）。据信B细胞会阻碍以T细胞为重点的现代免疫治疗策略的疗效。
这是一篇对截至2025年1月有关GBM中B细胞的现有证据的重点综述。
外周血反映出全身免疫反应受到抑制，表现为持续性淋巴细胞减少、浆细胞增多以及记忆B细胞功能失调。肿瘤免疫格局中B系细胞丰富。特征不明的B调节细胞（Breg）亚群存在于TME中，由于靠近MDSC、TAM和肿瘤细胞而形成其表型。Breg抑制CD8 T细胞活性，可能具有潜在的预后意义。
了解B细胞的作用、它们如何被募集以及它们向免疫调节作用的分化转变，可为更好的治疗策略提供依据，并在GBM中充分发挥其抗肿瘤潜力。
