Development of a mobile high-intensity focused ultrasound platform for preclinical tumor microenvironment modulation in a pancreatic ductal adenocarcinoma mouse model.

Abstract

Purpose: High-intensity focused ultrasound (HIFU) is a noninvasive ablation technology with increasing relevance for preclinical research and clinical translation. Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, with limited therapeutic options and poor response to current treatments, underscoring the urgent need for alternative strategies. To address this, we developed a mobile HIFU platform optimized for small-animal studies with an immersion-free design that improves usability while maintaining reproducible thermal ablation.

Materials and methods: The system was evaluated in a PDAC mouse model using KPC tumor cells. HIFU-induced tumor ablation and tumor growth were assessed, and histological and flow cytometric analyses were performed to evaluate treatment-assossiacted changes in the tumor microenvironment. To recapitulate the PDAC immune microenvironment in vitro, we further established a co-culture system of tumor organoids and CD8+ T cells.

Results: HIFU treatment induced tumor necrosis and significantly suppressed tumor growth. Histological and flow cytometric analyses revealed treatment-associated immune modulation, including increased proportions of activated CD8+ T cells, APC-like cells, and macrophage populations. In the organoid coculture model, activated CD8+ T cells accumulated around tumor organoids and were associated with increased tumor organoid death.

Conclusions: The proposed mobile HIFU system demonstrated reliable technical performance and biological efficacy in a preclinical PDAC model. This platform offers a practical tool for reproducible small-animal HIFU studies and highlights the potential of ultrasound-based tumor ablation as a strategy to address unmet therapeutic needs in pancreatic cancer.