Abstract
Cell-based immunotherapies have emerged as promising strategies for brain tumors, offering the potential for targeted and durable antitumor responses. However, their efficacy has been limited by challenges unique to the central nervous system, including suboptimal delivery routes and an immunosuppressive tumor microenvironment that impairs cell function. Focused ultrasound (FUS) is a noninvasive technology that, when combined with intravenously administered microbubbles, can transiently and reversibly increase blood-brain barrier permeability. FUS has improved drug delivery to brain tumors in clinical trials and offers compelling opportunities to enhance trafficking, activation, and control of therapeutic cells. Despite this potential, critical questions remain regarding the timing and sequencing of FUS with cell therapies, the impact of FUS on the tumor and neuroimmune microenvironments, strategies to mitigate acute and delayed toxicities, and methods to tune potency to maximize tumor specificity while minimizing bystander tissue injury. To address these challenges, the Focused Ultrasound Foundation convened a multidisciplinary roundtable in March 2025. Experts in neuro-oncology, neuroimmunology, cell therapy, neurosurgery, and FUS participated. Discussions focused on cell delivery routes, pharmacokinetics and blood-brain barrier opening, tumor microenvironment and CNS inflammation, FUS-induced immune modulation, clinical trial design, and approaches to safety monitoring and cell control. In this review, we summarize the discussions and key messages from the roundtable, which may serve as a foundation for advancing FUS-enhanced cell therapy for brain tumors in a collaborative manner.