Abstract
PURPOSE: Hepatic artery embolization is a locoregional treatment for hepatocellular carcinoma that may modulate the tumor immune microenvironment. However, its effects on tumor-infiltrating cluster of differentiation 8-positive lymphocytes remain unclear. This study evaluates changes in tumor-infiltrating cluster of differentiation 8-positive lymphocytes following hepatic artery embolization in an orthotopic rat hepatocellular carcinoma model using flow cytometry and immunohistochemistry. MATERIAL AND METHODS: Orthotopic hepatocellular carcinoma was established in rats using N1S1 cells. Animals were divided into an hepatic artery embolization group (n = 11) and a control group (n = 11). One week after the procedures, liver tumor tissues were harvested, and flow cytometry and immunohistochemistry were performed to quantify total and exhausted cluster of differentiation 8-positive lymphocytes. RESULTS: Tumor-infiltrating cluster of differentiation 8-positive lymphocytes significantly decreased in the hepatic artery embolization group compared to controls by both flow cytometry (0.13 ± 0.09 vs. 0.46 ± 0.27 × 10(6)/g, p < 0.01) and immunohistochemistry (14.67 ± 15.17 vs. 31.56 ± 20.98 cells/field of view, p < 0.05). However, the proportion of exhausted cluster of differentiation 8-positive lymphocytes by flow cytometry remained unchanged (8.24 ± 3.66% vs. 8.88 ± 2.60%, p = 0.72). CONCLUSIONS: Hepatic artery embolization reduces the number of tumor-infiltrating cluster of differentiation 8-positive lymphocytes without altering the proportion of exhausted T cells. These findings suggest that, to increase hepatic artery embolization efficacy in combination with immunotherapy, a strategy of recruiting more cluster of differentiation 8-positive lymphocytes into the tumor tissue may be necessary.