Abstract 3481: Transarterial embolization for HCC: how embolic agents shape tumor immunity and systemic responses

Abstract Transarterial embolization (TAE) is an effective therapy for hepatocellular carcinoma (HCC). Effects of the treatment on tumor immune microenvironment are poorly understood. Different TAE agents induce varying degrees of tumor and peritumoral hypoxia and nutrient-depletion. The purpose of this study is to investigate the immunological effects of the most commonly used embolic agents. Using a preclinical rat HCC model, tumors treated with oil or microspheres were compared to untreated controls. Tumor and serum samples collected at 7 and 14 days post-treatment were analyzed by flow cytometry, cytokine assays, and gene expression profiling using nanoString CodeSet. Ethiodized oil significantly altered the TME, reducing exhausted CD8+Tcells and PD-1+regulatory T cells while increasing CD45+CD3+immune cell infiltration (P≤0.05). Microsphere-treated tumors showed less pronounced effects. Serum cytokine analysis revealed a shift from Th2- to Th1-dominated immunity in the Ethiodized oil group, with elevated Th1 cytokines (IL-12,IL-18,IFNγ) and reduced Th2 cytokines (IL-4,IL-5,IL-10) at 14 days (P≤0.05). Both embolic agents reduced pro-inflammatory cytokines (IL-1α,IL-1β, TNFα,G-CSF), indicating a dampened systemic inflammatory response. Gene expression analysis showed significant downregulation of Th2-associated pathways, in tumors treated with Ethiodized oil. This treatment promoted a Th1-dominant immune response, contrasting with the Th2-skewed signaling seen in microsphere-treated tumors. Pathway analyses further demonstrated a reduced activity of Th2-associated chemokine receptors and cytokine pathways in Ethiodized oil-treated tumors compared to microspheres, highlighting distinct immunological modulations driven by embolic agent choice. The findings demonstrate how embolic agents impact the tumor microenvironment and systemic immunity. Ethiodized oil exhibits superior immunomodulatory effects, promoting a Th1 phenotype and reducing pro-tumoral factors. This information is critical for devising new combinatorial immunotherapy strategies in HCC that consider the distinct effects of different embolic agents. Citation Format: Andrea C. Cortes, Simone Anfossi, Kiyoyuki Minamiguchi, Rony Avritscher. Transarterial embolization for HCC: how embolic agents shape tumor immunity and systemic responses [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 3481.