Investigation of HIFU-induced anti-tumor immunity in a murine tumor model.
Investigation of HIFU-induced anti-tumor immunity in a murine tumor model.
复制标题
DOI：
10.1186/1479-5876-5-34
复制
发表时间：
2007-07-11
影响因子：
7.4
通讯作者：
Zhong, Pei
中科院分区：
文献类型：
--
作者：
Hu, Zhenlin;Yang, Xiao Yi;Liu, Yunbo;Sankin, Georgy N.;Pua, Eric C.;Morse, Michael A.;Lyerly, H. Kim;Clay, Timothy M.;Zhong, Pei
高强度聚焦超声（HIFU）是一种新兴的非侵入性癌症局部治疗方式。虽然目前的临床策略仅采用 HIFU 来对目标部位进行热消融，但与聚焦超声造成的热损伤和机械损伤相关的生物反应尚未得到彻底研究。特别是，来自 HIFU 损伤的肿瘤细胞的内源性危险信号可能会触发树突状细胞的激活。这种反应可能在 HIFU 引发的抗肿瘤免疫反应中发挥关键作用，可用于更有效的治疗。携带 MC-38 结肠腺癌肿瘤的小鼠接受热和机械 HIFU 暴露设置的治疗，以便独立观察 HIFU 诱导的对宿主免疫反应的影响。评估体内树突状细胞活性以及宿主对肿瘤生长的反应。研究发现，与单独 DC 注射观察到的 1.5 倍相比，热和机械 HIFU 分别使 CD11c+ 细胞增加了 3.1 倍和 4 倍。此外，热和机械 HIFU 分别使引流淋巴结中 CFSE+ DC 的积累增加了 5 倍和 10 倍。此外，聚焦超声治疗不仅可以减少原发肿瘤的生长，热 HIFU 的肿瘤体积减少了 85%，机械 HIFU 的肿瘤体积减少了 43%，而且还提供了针对皮下肿瘤再次攻击的保护。进一步的免疫学测定证实，经聚焦超声治疗的小鼠中，CTL 活性增强，肿瘤特异性 IFN-γ 分泌细胞增加，机械 HIFU 诱导的细胞毒性在效应器：靶标比例为 10:1 时高达 27%。这些研究呈现出初步令人鼓舞的结果，证实聚焦超声治疗可以引发全身抗肿瘤免疫反应，并且表明这种免疫与树突状细胞激活密切相关。由于当通过聚焦超声治疗机械裂解肿瘤细胞时，DC 激活更加明显，因此机械 HIFU 特别可以用作与随后的热消融相结合的潜在策略，通过增强宿主的抗肿瘤免疫力来提高 HIFU 癌症治疗的功效。
High intensity focused ultrasound (HIFU) is an emerging non-invasive treatment modality for localized treatment of cancers. While current clinical strategies employ HIFU exclusively for thermal ablation of the target sites, biological responses associated with both thermal and mechanical damage from focused ultrasound have not been thoroughly investigated. In particular, endogenous danger signals from HIFU-damaged tumor cells may trigger the activation of dendritic cells. This response may play a critical role in a HIFU-elicited anti-tumor immune response which can be harnessed for more effective treatment. Mice bearing MC-38 colon adenocarcinoma tumors were treated with thermal and mechanical HIFU exposure settings in order to independently observe HIFU-induced effects on the host's immunological response. In vivo dendritic cell activity was assessed along with the host's response to challenge tumor growth. Thermal and mechanical HIFU were found to increase CD11c+ cells 3.1-fold and 4-fold, respectively, as compared to 1.5-fold observed for DC injection alone. In addition, thermal and mechanical HIFU increased CFSE+ DC accumulation in draining lymph nodes 5-fold and 10-fold, respectively. Moreover, focused ultrasound treatments not only caused a reduction in the growth of primary tumors, with tumor volume decreasing by 85% for thermal HIFU and 43% for mechanical HIFU, but they also provided protection against subcutaneous tumor re-challenge. Further immunological assays confirmed an enhanced CTL activity and increased tumor-specific IFN-γ-secreting cells in the mice treated by focused ultrasound, with cytotoxicity induced by mechanical HIFU reaching as high as 27% at a 10:1 effector:target ratio. These studies present initial encouraging results confirming that focused ultrasound treatment can elicit a systemic anti-tumor immune response, and they suggest that this immunity is closely related to dendritic cell activation. Because DC activation was more pronounced when tumor cells were mechanically lysed by focused ultrasound treatment, mechanical HIFU in particular may be employed as a potential strategy in combination with subsequent thermal ablations for increasing the efficacy of HIFU cancer treatment by enhancing the host's anti-tumor immunity.
登录
查看更多内容
影响因子：
2.9
作者：
Chen, WS;Brayman, AA;Crum, LA
通讯作者：
Crum, LA
影响因子：
78.5
作者：
Kennedy, JE
通讯作者：
Kennedy, JE
DOI：
10.2217/14796694.2.1.111
发表时间：
2006-02-01
期刊：
Future oncology (London, England)
影响因子：
--
作者：
Frenkel, Victor;Li, King C P
通讯作者：
Li, King C P
影响因子：
2.9
作者：
Liu, Hao-Li;Chen, Wen-Shiang;Lin, Win-Li
通讯作者：
Lin, Win-Li
影响因子：
56.9
作者：
Matzinger, P
通讯作者：
Matzinger, P