Abstract 5547: Non-invasive monitoring of tumor biomechanics and implications for immunotherapy in HCC

Abstract

Abstract Shear-wave elastography (SWE) is a novel non-invasive technique used to quantify tissue stiffness. This approach can be used to longitudinally monitor tumor biomechanics and holds promise for guiding informed clinical decision-making. This study aims to explore the impact of tumor stiffness, as evaluated by SWE, on the proliferative potential of endothelial, tumor, and immune cells in a preclinical model of hepatocellular carcinoma. Tumor tissue sections from a Buffalo-McA-RH7777 rat HCC tumor model, utilizing a rat hepatoma cell line stably expressing green fluorescent protein genes (fluc/GFP) were selected based on the degree of tumor stiffness assessed by SWE. Nodules were separated based on mean shear wave values (3.05 versus 2.26 m/s) and categorized as stiff or soft, respectively. A 6-color panel was used to assess the percentages of different tumor, immune, and endothelial phenotypes in different areas of the tumor including immune cells (CD45+), endothelial cells (CD34+), green fluorescent protein (GFP), Ki67 (cell proliferation), and class-III intermediate filaments - vimentin. Our findings demonstrated increased expression of vimentin on immune cells (CD45+) within the tumor margin interphase. Stiffer tumors exhibited a higher percentage of CD45 cells co-expressing vimentin compared to softer tumors (P=0.01), whereas softer tumors showed an increased prevalence of CD34+ cells concurrently expressing Ki67 (P=0.01). Same pattern persisted in the tumor margin interphase regarding the proliferation of tumor cells identified by the expression of GFP co-expressing Ki67 (P<0.01). These findings highlight a significant association between tumor mechanical properties and the proliferative activity of endothelial and tumor cells, suggesting a link between tissue stiffness and the regulatory mechanisms associated with cellular proliferation and aggressiveness in HCC. Additionally, the presence of vimentin in immune cells may suggest that stiffer tumors may require enhanced migratory and invasive properties to compensate for changes in tumor mechanics thus potentially influencing immune function. Citation Format: Andrea C. Cortes, Kiyoyuki Minamiguchi, Hannah Kostan, Maria S. Stenkamp, Simone Anfossi, Natalie Wall Fowlkes, Rony Avritcsher. Non-invasive monitoring of tumor biomechanics and implications for immunotherapy in HCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5547.