Dromi Sergio A, Walsh Meghaan P, Herby Sarah, Traughber Bryan, Xie Jianwu, Sharma Karun V, Sekhar Kiran P, Luk Alfred, Liewehr David J, Dreher Matthew R, Fry Terry J, Wood Bradford J
Diagnostic Radiology Department, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Radiology. 2009 Apr;251(1):58-66. doi: 10.1148/radiol.2511072175. Epub 2009 Feb 27.
To evaluate the influence of subtotal radiofrequency (RF) ablation on a tumor-specific immune response in a murine tumor model and to explore the role of intratumoral dendritic cells (ITDCs) in mediating this effect.
Animal work was performed according to an approved protocol and in compliance with the National Cancer Institute Animal Care and Use Committee guidelines and regulations. A murine urothelial carcinoma (MB49) model expressing the male minor histocompatibility (HY) antigen was inoculated subcutaneously in female mice. Fourteen days later, splenic T cells were analyzed with enzyme-linked immunosorbent spot for HY immune response (n = 57). In subsequent experiments, mice were randomized into control (n = 7), RF ablation, ITDC (n = 9), and RF ablation + ITDC (n = 9) groups and monitored for tumor growth. Eleven days after treatment, tumors were harvested for histologic and immunohistochemical analysis. Animals demonstrating complete tumor regression were rechallenged in the contralateral flank.
Animals treated with subtotal RF ablation showed significant increases in tumor-specific class I and II responses to HY antigens and tumor regression. RF ablation, ITDC, and combined groups demonstrated similar levels of antigen-presenting cell infiltration; all groups demonstrated greater levels of infiltration compared with untreated controls. ITDC injection also resulted in tumor regression. However, combination therapy did not enhance tumor regression when compared with either treatment alone. Rechallenged mice in RF ablation, ITDC, and combination groups demonstrated significant tumor growth inhibition compared with controls.
Subtotal RF ablation treatment results in enhanced systemic antitumor T-cell immune responses and tumor regression that is associated with increased dendritic cell infiltration. ITDC injection mimics the RF ablation effect but does not increase immune responses when injected immediately after RF ablation.
评估在小鼠肿瘤模型中，部分射频（RF）消融对肿瘤特异性免疫反应的影响，并探讨肿瘤内树突状细胞（ITDCs）在介导这种效应中的作用。
动物实验按照批准的方案进行，并符合美国国立癌症研究所动物护理和使用委员会的指南及规定。将表达雄性次要组织相容性（HY）抗原的小鼠尿路上皮癌（MB49）模型皮下接种于雌性小鼠。14天后，用酶联免疫吸附斑点法分析脾T细胞的HY免疫反应（n = 57）。在随后的实验中，将小鼠随机分为对照组（n = 7）、射频消融组、ITDC组（n = 9）和射频消融+ITDC组（n = 9），并监测肿瘤生长情况。治疗11天后，采集肿瘤进行组织学和免疫组织化学分析。对显示肿瘤完全消退的动物在对侧腹侧再次接种肿瘤。
接受部分射频消融治疗的动物对HY抗原的肿瘤特异性I类和II类反应以及肿瘤消退均显著增加。射频消融组、ITDC组和联合治疗组的抗原呈递细胞浸润水平相似；与未治疗的对照组相比，所有组的浸润水平均更高。注射ITDC也导致肿瘤消退。然而，与单独任何一种治疗相比，联合治疗并未增强肿瘤消退效果。与对照组相比，射频消融组、ITDC组和联合治疗组再次接种肿瘤的小鼠显示出显著的肿瘤生长抑制。
部分射频消融治疗可增强全身抗肿瘤T细胞免疫反应和肿瘤消退，这与树突状细胞浸润增加有关。注射ITDC可模拟射频消融效应，但在射频消融后立即注射时不会增加免疫反应。
