The effect of HIFU treatment on liver metastasis of colorectal cancer in mice and its impact on immunity.

Abstract

3088 Background: The liver represents the predominant site for metastasis in colorectal cancer, with over 85% of cases exhibiting the microsatellite stable (MSS) phenotype, which typically shows limited response to immunotherapy. High-Intensity Focused Ultrasound (HIFU) not only facilitates direct destruction of tumor tissues but also has the potential to remodel the tumor immune microenvironment, thereby enhancing systemic anti-tumor immunity. This study aimed to explore the effects of HIFU on liver metastasis in a murine model and its subsequent impact on immune modulation. Methods: A BALB/c mice model of colorectal cancer liver metastasis was established and validated. The animals were treated with HIFU, followed by transcriptomic profiling and immunohistochemical staining to assess immune-related markers (CD8, F4/80, FOXP3, PD-L1, IL-6) in the liver metastasis tissues. Results: Transcriptomic sequencing performed on liver metastatic tissues collected seven days after HIFU treatment revealed a notable upregulation of CXCL14 expression, which was corroborated by protein immunoblotting. Immunohistochemical analysis demonstrated an increased infiltration of cytotoxic T cells (CD8+), a reduction in macrophage populations (F4/80), and a significant decrease in T regulatory cells (FOXP3 expression). Additionally, both PD-L1 and IL-6 levels were substantially reduced in the treated tissues. Conclusions: Seven days post-HIFU treatment, significant immune modulation was observed in liver metastatic tumor tissues, including enhanced infiltration of cytotoxic T cells, a reduction in immune-suppressive cell populations such as macrophages and Tregs, and the attenuation of inflammatory cytokines. These findings suggest that HIFU not only enhances the anti-tumor immune response but also facilitates the transition of liver metastases from an immune "cold" to a "hot" tumor microenvironment, potentially improving the efficacy of subsequent immunotherapeutic strategies.