Immune Effects of Cryoablation in Woodchuck Hepatocellular Carcinoma

作者：Michal Mauda‐Havakuk, Natalie Hawken, Joshua Owen, Andrew S. Mikhail, Matthew F. Starost, Baktiar Karim, Paul Wakim, Olga Lucía Franco-Mahecha, Andrew L. Lewis, William F. Pritchard, John W. Karanian, Bradford J. Wood · 发表于：Journal of Hepatocellular Carcinoma · 年份：2023 · DOI：10.2147/jhc.s426442 · 被引用次数：4 · 研究领域：Cancer Immunotherapy and Biomarkers、Hepatocellular Carcinoma Treatment and Prognosis、Cancer, Hypoxia, and Metabolism

Objectives: Local and systemic immune responses evoked by locoregional therapies such as cryoablation are incompletely understood. The aim of this study was to characterize cryoablation-related immune response and the capacity of immune drugs to augment immunity upon cryoablation for the treatment of hepatocellular carcinoma (HCC) using a woodchuck hepatocellular carcinoma model. Materials and Methods: Twelve woodchucks chronically infected with woodchuck hepatitis virus and with hepatocellular carcinoma underwent imaging with contrast-enhanced CT. Partial cryoablation of tumors in three woodchucks was performed. Fourteen days after cryoablation, liver tissues were harvested and stained with H&E and TUNEL, and immune infiltrates were quantified. Peripheral blood mononuclear cells (PBMC) were collected from ablated and nonablated woodchucks, labeled with carboxyfluorescein succinimidyl ester (CFSE) and cultured with immune-modulating drugs, including a small PD-L1 antagonist molecule (BMS-202) and three TLR7/8 agonists (DSR 6434, GS-9620, gardiquimod). After incubation, cell replication and immune cell populations were analyzed by flow cytometry. Results: Local immune response in tumors was characterized by an increased number of CD3+ T lymphocytes and natural killer cells in the cryolesion margin compared to other tumor regions. T regulatory cells were found in higher numbers in distant tumors within the liver compared to untreated or control tumors. Cryoablation also augment...