Focused ultrasound for enhancing cell-based immunotherapies in neuro-oncology

Cancers of the brain remain notoriously difficult to treat because of the unique and complex barriers imposed by the central nervous system and tumor microenvironment. Current therapeutic paradigms remain largely insufficient to achieve durable responses or cures. Cellular immunotherapies (CIs), including chimeric antigen receptor (CAR) T-cells and natural killer cell therapies, represent a new class of "living drugs" that harness endogenous or adoptively transferred immune cells to target and destroy cancer. Although transformative in hematologic malignancies, CIs have faced substantial barriers in solid tumors, particularly in the brain. Focused ultrasound (FUS), a noninvasive, nonionizing, and highly tunable platform for transcranial acoustic intervention, may help address these challenges through blood-brain barrier opening, vascular activation, immunologic reprogramming, and sonogenetic control. In this review, we systematically survey the current literature at the intersection of FUS and CIs in cancer, with emphasis on brain tumors and highlight key evidence supporting combinatorial strategies, immuno-imaging approaches for CI surveillance, and emerging translational opportunities-including a first-in-human clinical investigation in glioblastoma. We conclude with perspectives on how FUS may help enable safer, more effective, and more precise CI paradigms in neuro-oncology.