Gao, Peng, Cheng, Zhang, et al. found that surgically blocking the meningeal blood vessel hindered GBM progression in mice by restricting access to the dura mater by circulation-derived border-associated macrophages (cBAM). This reduced competition for CSF-1 and increasing expansion of resident BAMs (rBAMs), which showed enhanced antigen presentation and activation of antitumor T cells, dependent on their high expression of FcRn. The addition of CSF-1 or anti-PD-1 enhanced this antitumor effect. In patient samples, rBAM abundance correlated with increased intratumoral T cell activity and better survival outcomes.
Contributed by Lauren Hitchings
ABSTRACT: The dura mater, the outermost meningeal layer that samples and presents central nervous system (CNS)-derived antigens, is a pivotal interface for CNS immunosurveillance. Here, we show that meningeal blood vessel blockage effectively suppresses glioblastoma (GBM) progression in murine models. Single-cell profiling of dura reveals a resident border-associated macrophage (rBAM) subset characterized by high neonatal Fc receptor expression, which endows rBAMs with superior capacity for presenting tumor antigens and activating CNS-patrolling T cells. Meningeal blood vessel blockage preserves dural cerebrospinal fluid (CSF)-1 levels by restricting circulation-derived BAM (cBAM) and expands the rBAM pool, thereby enhancing T cell activation at the dura interface and amplifying intratumoral cytotoxic T cell responses. Clinically, rBAM abundance positively correlates with GBM patient survival. Our findings show that the dura is a critical regulator of anti-tumor immunity in CNS cancers and propose that meningeal blood vessel blockage may be a surgical strategy to potentiate GBM immunotherapy.
Author Info: (1) Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China; Guangdong Provincial Key Laboratory of Brain Function a
Author Info: (1) Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, Guangdong, China. (2) Biomedical Pioneering Innovation Center (BIOPIC), Peking-Tsinghua Center for Life Sciences (CLS), School of Life Sciences, Peking University (PKU), Beijing, China; Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing, China. (3) Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, Guangdong, China. (4) Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, Guangdong, China. (5) Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, Guangdong, China. (6) Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China. (7) Biomedical Pioneering Innovation Center (BIOPIC), Peking-Tsinghua Center for Life Sciences (CLS), School of Life Sciences, Peking University (PKU), Beijing, China; Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing, China. (8) Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, Guangdong, China. (9) Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, Guangdong, China. (10) Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, Guangdong, China. (11) Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, Guangdong, China. (12) Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, Guangdong, China. (13) Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, Guangdong, China. (14) Department of Scientific Research Section, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China. (15) National Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, Jiangsu, China. (16) Biomedical Pioneering Innovation Center (BIOPIC), Peking-Tsinghua Center for Life Sciences (CLS), School of Life Sciences, Peking University (PKU), Beijing, China; Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing, China. Electronic address: fbai@pku.edu.cn. (17) Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, Guangdong, China. Electronic address: zhangnu2@mail.sysu.edu.cn.
