Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University, Chongqing, China.
Ultrasound Med Biol. 2010 Mar;36(3):441-8. doi: 10.1016/j.ultrasmedbio.2009.12.004.
Previous studies have shown that high-intensity focused ultrasound (HIFU) ablation can induce a local inflammation with marked infiltration of dendritic cells (DCs). The purpose of this study was to investigate whether DCs could capture and present activating signals delivered by necrotic tumour cells that remain in situ after HIFU, thus initiating specific antitumour immunity. Tumour debris was derived from a mouse H22 tumour model after HIFU ablation. Bone marrow-derived DCs were loaded with HIFU-treated tumour, tumour lysate and mouse serum. Syngeneic naïve C57BL/6J mice were immunised with three loaded DCs followed by a subsequent H22 tumour challenge. Tumour size and survival were then recorded in each vaccinated mouse. The results showed that both HIFU-ablated tumour and tumour lysate could significantly increase the number of mature DCs and the secretion of IL-12 and IFN-gamma (p<0.001). The proliferation of splenic lymphocytes co-incubated with the loaded-DCs was significantly higher in both HIFU-ablated tumour and tumour lysate groups (p<0.01). Cytotoxocity and TNF-alpha and IFN-gamma secretion of cytotoxic T lymphocytes against H22 cells were significantly higher in HIFU-ablated tumour group than that in tumour lysate group (p<0.01). After the H22 tumour challenge, a significant decrease of tumour volume was observed in HIFU-ablated tumour group (p<0.01). However, there was no statistical difference of long-term survival rates among three groups (p>0.05). It is concluded that DCs can be activated by HIFU-ablated tumour debris and, thus, initiate host specific antitumour immune response after HIFU therapy.
先前的研究表明，高强度聚焦超声（HIFU）消融会引起局部炎症，伴有树突状细胞（DC）的明显浸润。本研究旨在探讨 DC 是否能捕获和呈递原位 HIFU 后残留的坏死肿瘤细胞传递的激活信号，从而引发特异性抗肿瘤免疫。肿瘤碎片来源于 HIFU 消融后的小鼠 H22 肿瘤模型。用 HIFU 处理的肿瘤、肿瘤裂解物和小鼠血清负载骨髓来源的 DC。用三种负载 DC 对同基因 naive C57BL/6J 小鼠进行免疫接种，然后用 H22 肿瘤进行后续挑战。然后记录每个接种小鼠的肿瘤大小和存活情况。结果表明，HIFU 消融的肿瘤和肿瘤裂解物均能显著增加成熟 DC 的数量和 IL-12 和 IFN-γ的分泌（p<0.001）。与负载-DC 共孵育的脾淋巴细胞的增殖在 HIFU 消融的肿瘤和肿瘤裂解物组中均显著升高（p<0.01）。针对 H22 细胞的细胞毒性 T 淋巴细胞的细胞毒性、TNF-α 和 IFN-γ分泌在 HIFU 消融的肿瘤组中明显高于肿瘤裂解物组（p<0.01）。在 H22 肿瘤挑战后，在 HIFU 消融的肿瘤组中观察到肿瘤体积显著减少（p<0.01）。然而，三组之间的长期生存率没有统计学差异（p>0.05）。结论是，HIFU 消融的肿瘤碎片可以激活 DC，并在 HIFU 治疗后引发宿主特异性抗肿瘤免疫反应。
