Histotripsy has an abscopal effect and induces an adaptive immune response in a neuroblastoma syngeneic model

Background: Over 50% of high-risk neuroblastoma (NB) patients fail to respond to treatment. Histotripsy, a focused ultrasound therapy under development for nonthermal-tissue ablation via bubble activity, can ablate NB xenograft tumors and induce apoptosis. Reports suggest histotripsy may turn cold tumors to be immune responsive: we hypothesized that histotripsy can activate an immune response and an abscopal effect (distal tumor targeting). Methods: NB neuro-2a cells were bilaterally injected subcutaneously on each flank of immunocompetent mice. Histotripsy was applied to approximately 80% of one tumor with a custom system. Untreated controls received no treatment. Tumor volumes were calculated using the ellipsoidal formula from caliper measurements. After 6 days, single-cell suspensions were fixed and interrogated via flow cytometry using immune cell markers. n = 4–6 per group. Results: By day 5, untreated controls were twofold larger than histotripsy-treated tumors (p = 0.03) as well as their contralateral tumors. Flow cytometry revealed that immune cell markers such as CD3 + CD4 + T cells, F4/80 + macrophages, and CD11b + granulocytes were higher in both histotripsy and contralateral tumors compared to untreated controls (p < 0.05). Conclusions: Histotripsy delays tumor growth and has an abscopal effect on this NB model and activates an immune response.