Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois; Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, Illinois; Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, Illinois.
J Vasc Interv Radiol. 2024 Jul;35(7):1033-1042.e11. doi: 10.1016/j.jvir.2024.03.014. Epub 2024 Mar 19.
To investigate immuno-ethanol ablation using an ethanol and immune adjuvant formulation as a potent immunoablation approach that can achieve an enhanced anticancer effect in the treatment of hepatocellular carcinoma (HCC).
Ethanol concentration- and exposure time-dependent cellular responses were investigated. Curcumin was combined with ethanol as an immunoablation agent. Cellular uptake of curcumin, cancer cell killing, and inflammatory markers of ethanol-curcumin treatment were characterized. To evaluate the potential in vivo anticancer immunity of ethanol-curcumin treatment, each right and left lobe of rat liver was concurrently inoculated with N1S1 HCC cells and a mixture of treated N1S1 cells (ethanol only or ethanol-curcumin) in Sprague Dawley rats (each group: 5 rats; control: nontreated N1S1 cells). Tumor growth and immune response were characterized with 7T magnetic resonance (MR) imaging, flow cytometry analysis, and immunohistology.
An optimized ethanol-curcumin (10% ethanol and 0.5% weight/volume (w/v) curcumin solution) treatment contributed to an enhanced cellular uptake of curcumin, increased cancer cell killing, and decreased inflammatory reaction. Ethanol-curcumin-treated N1S1 cell implantation in the rat liver demonstrated N1S1 HCC tumor rejection. The secondary tumor growth by nontreated N1S1 cell inoculation was significantly suppressed at the same time. Activated anticancer immunity was evidenced by significantly increased CD8 T cell infiltration (3.5-fold) and CD8-to-regulatory T cell ratio (4.5-fold) in the experimental group compared with those in the control group.
Enhanced anticancer effect of immuno-ethanol ablation could be achieved with ethanol-curcumin agent. The results underscore the importance of optimized immunoablation therapeutic procedures for enhanced therapeutic outcomes.
研究使用乙醇和免疫佐剂制剂进行免疫乙醇消融，作为一种有效的免疫消融方法，可在治疗肝细胞癌 (HCC) 中实现增强的抗癌效果。
研究了乙醇浓度和暴露时间依赖性的细胞反应。将姜黄素与乙醇联合用作免疫消融剂。研究了姜黄素的细胞摄取、癌细胞杀伤和乙醇-姜黄素处理的炎症标志物。为了评估乙醇-姜黄素治疗的潜在体内抗癌免疫，将每只大鼠的左右肝叶同时接种 N1S1 HCC 细胞和用乙醇（仅乙醇或乙醇-姜黄素）处理的 N1S1 细胞混合物（每组：5 只大鼠；对照：未处理的 N1S1 细胞）。通过 7T 磁共振 (MR) 成像、流式细胞术分析和免疫组织化学评估肿瘤生长和免疫反应。
优化的乙醇-姜黄素（10%乙醇和 0.5%重量/体积 (w/v) 姜黄素溶液）处理有助于增强姜黄素的细胞摄取、增加癌细胞杀伤和减少炎症反应。在大鼠肝脏中植入乙醇-姜黄素处理的 N1S1 细胞可导致 N1S1 HCC 肿瘤排斥。同时，未处理的 N1S1 细胞接种引起的继发性肿瘤生长明显受到抑制。实验组 CD8 T 细胞浸润（增加 3.5 倍）和 CD8 调节性 T 细胞比值（增加 4.5 倍）明显高于对照组，表明激活了抗癌免疫。
使用乙醇-姜黄素剂可以实现免疫乙醇消融的增强抗癌效果。研究结果强调了优化免疫消融治疗程序对于提高治疗效果的重要性。
