Key Points
- The project evaluated histotripsy as a new treatment for high-risk pediatric neuroblastoma.
- The intervention significantly delayed tumor growth and created a systemic immune effect, especially when combined with chemotherapy.
The results from a pediatric preclinical research project that was co-funded by the Foundation along with the Arms Wide Open Childhood Cancer Foundation (AWOCCF) have now been published. AWOCCF is a non-profit organization that funds pediatric cancer research, supports families both financially and emotionally, educates the general public, and raises awareness globally, among many other programs and community-building events for the greater childhood cancer community.
The research was seeking new solutions for treating high-risk pediatric neuroblastoma, a pediatric cancer with poor outcomes and frequent metastatic disease. Histotripsy is a noninvasive focused ultrasound therapy that mechanically disrupts tumors with cavitation bubble clouds.
Histotripsy-Initiated Immune Response Synergizes with Chemotherapy in a Neuroblastoma Murine Model
Led by Kenneth B. Bader, PhD, and Sonia L. Hernandez, PhD, at the University of Chicago, the study investigated whether histotripsy could enhance global anti-tumor immunity in a model of metastatic disease and improve chemotherapy response in high-risk neuroblastoma.
Using a bilateral syngeneic mouse model of neuroblastoma, investigators treated one tumor with histotripsy alone or in combination with liposomal doxorubicin (LDOX), while the untreated contralateral tumor served as a model of distant metastatic disease. The team monitored tumor growth and conducted flow cytometry, immunohistochemistry, and single-cell RNA sequencing to evaluate both local and systemic immune responses.
Histotripsy significantly delayed growth of both treated and untreated tumors, indicating a systemic immune effect. The tumor microenvironment was found to have an increased infiltration of cytotoxic CD8⁺ T cells and inflammatory myeloid cells. The tumors also showed other signs of broad immune-mediated metabolic reprogramming, including a reduction in neuroblastoma cell proliferation activity.
Most importantly, combining histotripsy with LDOX produced the greatest tumor growth suppression and immune activation, which supports the concept that histotripsy can convert immunologically “cold” tumors into more responsive ones and potentiate standard chemotherapy in metastatic neuroblastoma.
Next steps include further defining the immune mechanisms underlying histotripsy-induced systemic responses, optimizing combination strategies with chemotherapy or immunotherapy, and advancing toward translational studies to support clinical evaluation in high-risk neuroblastoma.
See MDPI Cancers (Open Access)
This publication was included in MDPI Cancers special issue on Ultrasound for Cancer Therapy, where the journal is highlighting preclinical and clinical research advancing ultrasound as a noninvasive tool for cancer treatment. The issue is being edited by Zhen Xu, PhD, and Natasha Sheybani, PhD, and submissions are being accepted through June 30, 2026.
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