Focused ultrasound effects on the glioblastoma immune microenvironment

Abstract

Focused ultrasound (FUS) is an attractive method of treating neurological diseases, such as glioblastoma (GBM). An accumulating body of evidence has confirmed the efficacy and safety of using FUS with systematically circulating microbubbles, which operate as acoustic enhancers, to temporarily open the blood-brain barrier for drug delivery. However, there is very limited knowledge of how immune cell respond to mechanical stimuli such as FUS, particularly in the complex immune microenvironments of brain tumors. Here, we report FUS immunomodulation effects may also include the enhanced recruitment and activation of other mononuclear phagocytes in murine models of GBM in tests with or without monoclonal antibody-based passive immunotherapy. Flow cytometry, immunohistochemistry, and in vitro cell co-culture studies were performed for immunoprofiling and immune effector determination. In murine GBM models, our results demonstrated that FUS enhanced antigen presentation behaviors of tumor-associated macrophages without affecting the microglia. FUS also reprogrammed the macrophages locally towards the anti-cancer phenotype. Taken together, our results offer new evidence in FUS immunomodulation on the myeloid compartment of the brains in GBM mouse models.