Skull-meninges-brain connectivity and extra-axial brain tumours.

The cortex of the brain is covered by three meningeal layers: the dura, the arachnoid, and the pia mater. Substantial discoveries have been made demonstrating the structural and functional relationships between these layers, and with other neighbouring structures such as the skull. Importantly, improved understanding of the meningeal lymphatic network places the meninges at the nexus of a cross talk between the brain, peripheral immune system, and the skull bone marrow. The meningeal lymphatic network has been shown to regulate immune responses in models of health and disease states, such as intra-axial brain tumours, affecting a tumour's behaviour. Unsurprisingly, a diverse array of resident and circulating immune cells such as macrophages, T-cells and B-cells can be found in the meninges, with specialized organizations or hubs surrounding the dural venous sinuses and cranial nerves. Meningioma and vestibular schwannoma are the most common extra-axial brain tumours, with varying clinical courses related to their immune microenvironments. These tumours commonly occur in proximity to the immune hubs of the meninges. This could point towards a possible bidirectional interaction, not only implicated in regulating tumour immune cell infiltration, but also meningeal inflammation and symptoms such as headaches and anxiety. This review will summarize the meningeal structure and function and highlight how these may be linked to patients with meningioma or vestibular schwannoma.