Meningeal blood vessel blockage enhances anti-glioblastoma immunity.

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 colony-stimulating factor 1 (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.