Meningeal immunity and “Interstitial” therapy: a new paradigm for immunotherapy in glioblastoma

Glioblastoma (GBM) is one of the most aggressive brain tumors, and its immunotherapy faces significant challenges, including the physical barrier of the blood-brain barrier, the tumor immunosuppressive microenvironment, and the difficulty of effective immune cell infiltration into tumor tissue. In recent years, the anatomical and functional basis of the meningeal immune system has been gradually revealed, particularly the discovery of the dural lymphatic system and tissue-resident border-associated macrophages (rBAMs), providing new insights for GBM immunotherapy. "Interstitial" immunotherapy, as an innovative strategy, emphasizes a shift from the traditional focus on the tumor interior to the tumor "border," leveraging the unique advantages of the meningeal immune system to enhance the effectiveness of immune responses. This review systematically examines the current status and dilemmas of GBM immunotherapy, the anatomical and functional basis of meningeal immunity, the discovery and mechanisms of rBAMs, the theoretical implications of "interstitial" immunotherapy, and the clinical translation prospects and challenges of this strategy, aiming to provide new theoretical support and practical guidance for GBM immunotherapy.