Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
Department of Radiology, IVR Center, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan.
Cardiovasc Intervent Radiol. 2020 Feb;43(2):311-321. doi: 10.1007/s00270-019-02343-1. Epub 2019 Oct 7.
To determine the tumor immune cell landscape after transcatheter arterial bland embolization (TAE) in a clinically relevant rat hepatocellular carcinoma (HCC) model.
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.
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).
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.
在临床相关大鼠肝细胞癌（HCC）模型中，确定经导管动脉栓塞（TAE）后肿瘤免疫细胞的特征。
21 只植入同源 McArdle RH-7777 大鼠肝癌细胞的水牛大鼠，左肝叶接受 TAE 治疗，使用 70-150μm 微球（n=9）或肝动脉生理盐水输注（n=12）。TAE 治疗后 14 天，收集 HCC 结节、肿瘤边缘、相邻非癌性肝组织和脾脏实质，制成单细胞悬液，进行免疫特征分析。通过多参数流式细胞术评估肿瘤浸润免疫亚群的变化，包括 CD4 T 细胞（Th17 和 Treg）、CD8 细胞毒性 T 细胞（IFNγ）和中性粒细胞。在模拟栓塞后环境（即缺氧和营养缺乏）的条件下，通过 IL-17 迁移和集落形成实验，研究 Th17 细胞特征性细胞因子 IL-17 对 McArdle RH-7777 肝癌细胞的影响。采用学生独立 t 检验或单因素方差分析确定统计学意义。
与对照组相比，TAE 治疗后 14 天，肝脏肿瘤中 Th17 细胞浸润增加（0.29±0.01 比 0.19±0.02；p=0.02）。在脾脏中也观察到类似的模式（1.41±0.13 比 0.57±0.08；p<0.001），表明存在局部和全身效应。各组间 FoxP3+Treg、IFNγ 产生的 CD4 T 细胞和 CD8 T 细胞的百分比无显著差异（p>0.05）。栓塞后体外实验表明，IL-17 在 24-48 小时降低 McA-RH7777 细胞的迁移（p=0.003 和 p=0.002）。
经导管肝动脉栓塞术可诱导局部和全身 Th17 细胞浸润增加，并表达其特征性细胞因子 IL-17。在模拟栓塞后环境中，IL-17 显著降低了 McA-RH7777 细胞的迁移。
