PURPOSE To determine the tumor immune cell landscape after transcatheter arterial bland embolization (TAE) in a clinically relevant rat hepatocellular carcinoma (HCC) model. MATERIALS AND METHODS Buffalo rats (n = 21) bearing syngeneic McArdle RH-7777 rat hepatoma cells implanted into the left hepatic lobe underwent TAE using 70-150 µm beads (n = 9) or hepatic artery saline infusion (n = 12). HCC nodules, peritumoral margin, adjacent non-cancerous liver, and splenic parenchyma were collected and disaggregated to generate single-cell suspensions for immunological characterization 14 d after treatment. Changes in tumor-infiltrating immune subsets including CD4 T cells (Th17 and Treg), CD8 cytotoxic T cells (IFNγ), and neutrophils were evaluated by multiparameter flow cytometry. Migration and colony formation assays were performed to examine the effect of IL-17, a signature cytokine of Th17 cells, on McArdle RH-7777 hepatoma cells under conditions simulating post-embolization environment (i.e., hypoxia and nutrient privation). Statistical significance was determined by the Student unpaired t test or one-way ANOVA. RESULTS TAE induces increased infiltration of Th17 cells in liver tumors when compared with controls 14 d after treatment (0.29 ± 0.01 vs. 0.19 ± 0.02; p = 0.02). A similar pattern was observed in the spleen (1.41 ± 0.13 vs. 0.57 ± 0.08; p < 0.001), indicating both local and systemic effect. No significant differences in the percentage of FoxP3 + Tregs, IFNγ-producing CD4 T cells, and CD8 T cells were observed between groups (p > 0.05). In vitro post-embolization assays demonstrated that IL-17 reduces McA-RH7777 cell migration at 24-48 h (p = 0.003 and p = 0.002, respectively). CONCLUSION Transcatheter hepatic arterial bland embolization induces local and systemic increased infiltration of Th17 cells and expression of their signature cytokine IL-17. In a simulated post-embolization environment, IL-17 significantly reduced McA-RH7777 cell migration.

中文翻译：

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在肝细胞癌的同系大鼠模型中，肝动脉无栓塞栓塞增加了Th17细胞的浸润。

目的确定在临床相关的大鼠肝细胞癌（HCC）模型中经导管动脉无栓塞（TAE）后的肿瘤免疫细胞格局。材料与方法将具有同系McArdle RH-7777大鼠肝癌细胞的布法罗大鼠（n = 21）植入左肝叶，使用70-150 µm磁珠（n = 9）或肝动脉生理盐水输注（n = 12）进行TAE。收集HCC结节，肿瘤周缘，邻近的非癌性肝和脾实质，并在处理后14 d进行分解，以产生用于免疫学表征的单细胞悬液。通过多参数流式细胞术评估包括CD4 T细胞（Th17和Treg），CD8细胞毒性T细胞（IFNγ）和中性粒细胞的肿瘤浸润免疫亚群的变化。在模拟栓塞后环境（即缺氧和营养缺乏）的条件下，进行了迁移和集落形成试验，以检查IL-17（Th17细胞的标志性细胞因子）对McArdle RH-7777肝癌细胞的影响。统计显着性由学生未配对t检验或单向方差分析确定。结果与治疗后14 d相比，TAE诱导了Th17细胞在肝肿瘤中的浸润增加（0.29±0.01 vs. 0.19±0.02； p = 0.02）。在脾脏中观察到类似的模式（1.41±0.13 vs. 0.57±0.08； p <0.001），表明局部和全身作用。在各组之间，没有观察到FoxP3 + Treg，产生IFNγ的CD4 T细胞和CD8 T细胞百分比的显着差异（p> 0.05）。体外栓塞后测定表明，IL-17在24-48 h时可降低McA-RH7777细胞迁移（分别为p = 0.003和p = 0.002）。结论经导管肝动脉平淡栓塞可诱导Th17细胞局部和全身浸润增加以及其标志性细胞因子IL-17的表达。在模拟的栓塞后环境中，IL-17显着减少了McA-RH7777细胞迁移。