In this context, the central hypothesis is that dysfunction of the glymphatic and immune barriers co-contributes to the therapeutic resistance of GBM: glymphatic dysfunction and disruption of the BBB (often correlated with mislocalization of AQP4) restrict the penetration of therapeutic agents and compromise the drainage of tumor antigens toward the meningeal lymphatic vessels (MLVs) [4]. Here, AQP4 is linked to neoplasm.