Abstract 3466: Bubble therapy: Histotripsy ablation of pancreatic tumors in an <i>in vivo</i> murine model affects the tumor microenvironment and increases systemic anti-tumor immunity

Abstract Pancreatic cancer is one of the leading causes of cancer-related deaths, highlighting the urgent need for innovative treatment strategies. Histotripsy is a non-invasive, non-ionizing, non-thermal, image-guided focused ultrasound ablation treatment method that uses high-pressure pulses to create acoustic cavitation, a “bubble cloud, ” at the target. The rapid expansion and collapse of this bubble cloud ablates the tumor into an acellular homogenate. In this study, we evaluated the hypothesis that histotripsy ablation of pancreatic tumors reduces tumor burden, activates systemic immune responses, and induces an abscopal-like effect. Our in-vivo study is a contralateral study conducted in C57BL/6J mice, employing a specialized histotripsy setup designed for precision. This setup featured a customized 1 MHz, 8-element histotripsy transducer engineered with a tailored focal point geometry. We targeted partial ablation around 50-60% to activate the immune responses and convert the “cold” pancreatic tumor microenvironment to “hot” tumor microenvironment. Treatment parameters included a peak negative pressure (PNP) of 250 Hz, a pulse repetition frequency (PRF) of 250 Hz, and 250 pulses per focal point. Mice were harvested in 5 groups/timepoints (2 hours, 24 hours, 7 days, 14 days and 21 days), with biological assessments generally focused on ablation zone, structural effects of histotripsy, chemokines and cytokines released and immune cell populations. The study’s significance lies in understanding how histotripsy influences immune responses, particularly T cell infiltration and proliferation, from the treated tumor site to the untreated contralateral tumor site. Our data demonstrated that histotripsy effectively reduced tumor volume, with significant reductions in tumor diameter observed in both treated and contralateral untreated tumors compared to control groups. Flow cytometry analysis revealed significant changes in immune cell populations across treated and control groups. Transcriptomic analyses identified differentially expressed genes and pathways associated with systemic anti-tumor immune responses, while mass spectrometry highlighted antigens presented by antigen-presenting cells. Overall, the results indicated that histotripsy promotes a localized immune response, leading to immune system activation and substantial alterations in the tumor microenvironment. These systemic immunological changes present potential targets for adjuvant therapies, underscoring the promise of histotripsy as a therapeutic modality in pancreatic cancer treatment. Citation Format: Tamalika Paul, Victor Lopez, Cora Youngs, Carley Elliott, K.M Imran, Tyler Moore, Manali Powar, Benjamin Tintera, Eli Vlaisavljevich, Irving Coy Allen. Bubble therapy: Histotripsy ablation of pancreatic tumors in an in vivo murine model affects the tumor microenvironment and increases systemic anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3466.