Histotripsy-Initiated Immune Response Synergizes with Chemotherapy in a Neuroblastoma Murine Model

BACKGROUND: High-risk neuroblastoma (NB) is a pediatric malignancy associated with metastases and an immunosuppressive tumor microenvironment. Standard-of-care treatments like chemotherapy are often ineffective, which motivates the investigation of adjuvant approaches. Histotripsy is a noninvasive focused ultrasound therapy that ablates tissue through the mechanical action of bubble clouds. In addition to disruption of the targeted tumor, non-targeted lesions may exhibit growth delay after the histotripsy procedure. The primary hypothesis of this study was histotripsy-induced shifts in the tumor microenvironment will improve the response of metastatic NB to chemotherapy. METHODS: ), with or without concurrent administration of liposomal doxorubicin (LDOX). The contralateral tumor served as a model of non-targeted distal metastases. Following treatment, tumors were monitored indefinitely for growth, or assessed after 5-7 days with flow cytometry, single-cell RNA sequencing, and immunohistochemistry. RESULTS: and MOMA staining. CONCLUSIONS: These findings indicate that histotripsy induces a systemic antitumor immune response that potentiates chemotherapy efficacy in this model of metastatic NB.