Mechanistic and imaging evidence discussed throughout this review supports a graded model in which progressive impairment of CSF-ISF exchange, increased intracranial pressure, AQP4 depolarisation, vasogenic edema, and restricted meningeal lymphatic drainage incrementally limit tumor antigen egress and immune priming, thereby reducing the likelihood and magnitude of response to immune checkpoint inhibitors [4,5,6,18,45,46]. This evidence concerns the gene AQP4 and neoplasm.