Investigation of the Potential Immunological Effects of Boiling Histotripsy for Cancer Treatment

Abstract

Boiling histotripsy (BH) is a completely non-invasive ultrasonic technique that can be used to mechanically destroy tumor tissues. Studies have shown that BH has biological effects on immune responses, but the mechanisms involved in the induction and enhancement of systemic anti-tumor immune responses after BH treatment are poorly understood. The present study therefore investigates the anti-tumor immune responses triggered by BH exposure in vivo. In a syngeneic tumor model, BH treatment results in more dendritic cell maturation and increased intra-tumoral infiltration of activated CD8+ T？cells compared to those observed after thermal high-intensity focused ultrasound exposure. The results clearly show that tumor antigens and danger signals released after BH exposure can lead to a sufficient anti-tumor immune response with antigen-presenting cell activation. In the 4T1 triple-negative breast cancer model, BH-induced mechanical ablation further enhances the therapeutic effect of immune checkpoint blockade, indicating a synergistic anti-tumor immune effect. In conclusion, the results presented in this study suggest that BH is a promising option for boosting anti-tumor immunity and can be beneficially combined with cancer immunotherapy. ？ 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim