Boosting high-intensity focused ultrasound-induced anti-tumor immunity using a sparse-scan strategy that can more effectively promote dendritic cell maturation.
Boosting high-intensity focused ultrasound-induced anti-tumor immunity using a sparse-scan strategy that can more effectively promote dendritic cell maturation.
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使用稀疏扫描策略增强高强度聚焦超声诱导的抗肿瘤免疫，可以更有效地促进树突状细胞成熟
DOI：
10.1186/1479-5876-8-7
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发表时间：
2010-01-27
影响因子：
7.4
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Liu F;Hu Z;Qiu L;Hui C;Li C;Zhong P;Zhang J
高强度聚焦超声(HIFU)治疗中的常规治疗方案利用密集扫描策略来产生紧密堆积的热损伤，旨在尽可能地根除肿瘤块。然而，这种策略在诱导系统抗肿瘤免疫方面并不是最有效的，因此它不能提供有效的微转移控制和长期的肿瘤耐药。我们先前提供的证据表明，HIFU可能通过原位激活经HIFU治疗的肿瘤组织内的树突状细胞(DC)来增强全身抗肿瘤免疫。本研究旨在测试稀疏扫描策略通过更有效地促进DC成熟来增强HIFU诱导的抗肿瘤免疫反应的可行性。建立了一个实验性的HIFU系统，用于对皮下移植的MC-38和B16肿瘤进行密集或稀疏扫描的肿瘤消融实验，以产生紧密堆积或分离的热损伤。免疫组织化学和流式细胞术检测HIFU治疗后肿瘤组织中DC的浸润情况。经不同HIFU处理的肿瘤细胞与DC共培养后，通过IL-12/IL-10的产生和CD80/CD86的表达来评价DC的成熟。通过检测HIFU对远距离再攻击肿瘤的生长抑制作用和肿瘤特异性干扰素-γ分泌细胞来评价HIFU诱导的抗肿瘤免疫反应。在S的实验肿瘤中，HIFU照射将束流焦点处的温度提高到80摄氏度，并导致形成明确的热损伤。在HIFU照射期间，被渗透的DC被招募到病变周围，那里的峰值温度只有55摄氏度。肿瘤细胞在4-S高强度聚焦超声照射下加热至55℃时，可更有效地刺激共培养的DC成熟。稀疏扫描HIFU可以在分离的病灶周围保留55度加热的肿瘤细胞，比密集扫描HIFU能诱导更强的抗肿瘤免疫反应，而对治疗后的原发肿瘤的抑制作用保持在相同的水平。流式细胞仪分析表明，稀疏扫描HIFU较密集扫描HIFU能更有效地促进DC向肿瘤组织的浸润，促进肿瘤组织的原位成熟。优化扫描策略是通过更有效地促进DC成熟来增强HIFU诱导的抗肿瘤免疫的可行途径。
The conventional treatment protocol in high-intensity focused ultrasound (HIFU) therapy utilizes a dense-scan strategy to produce closely packed thermal lesions aiming at eradicating as much tumor mass as possible. However, this strategy is not most effective in terms of inducing a systemic anti-tumor immunity so that it cannot provide efficient micro-metastatic control and long-term tumor resistance. We have previously provided evidence that HIFU may enhance systemic anti-tumor immunity by in situ activation of dendritic cells (DCs) inside HIFU-treated tumor tissue. The present study was conducted to test the feasibility of a sparse-scan strategy to boost HIFU-induced anti-tumor immune response by more effectively promoting DC maturation. An experimental HIFU system was set up to perform tumor ablation experiments in subcutaneous implanted MC-38 and B16 tumor with dense- or sparse-scan strategy to produce closely-packed or separated thermal lesions. DCs infiltration into HIFU-treated tumor tissues was detected by immunohistochemistry and flow cytometry. DCs maturation was evaluated by IL-12/IL-10 production and CD80/CD86 expression after co-culture with tumor cells treated with different HIFU. HIFU-induced anti-tumor immune response was evaluated by detecting growth-retarding effects on distant re-challenged tumor and tumor-specific IFN-γ-secreting cells in HIFU-treated mice. HIFU exposure raised temperature up to 80 degrees centigrade at beam focus within 4 s in experimental tumors and led to formation of a well-defined thermal lesion. The infiltrated DCs were recruited to the periphery of lesion, where the peak temperature was only 55 degrees centigrade during HIFU exposure. Tumor cells heated to 55 degrees centigrade in 4-s HIFU exposure were more effective to stimulate co-cultured DCs to mature. Sparse-scan HIFU, which can reserve 55 degrees-heated tumor cells surrounding the separated lesions, elicited an enhanced anti-tumor immune response than dense-scan HIFU, while their suppressive effects on the treated primary tumor were maintained at the same level. Flow cytometry analysis showed that sparse-scan HIFU was more effective than dense-scan HIFU in enhancing DC infiltration into tumor tissues and promoting their maturation in situ. Optimizing scan strategy is a feasible way to boost HIFU-induced anti-tumor immunity by more effectively promoting DC maturation.
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影响因子：
5.8
作者：
Satthaporn, S;Robins, A;Eremin, O
通讯作者：
Eremin, O
影响因子：
3.4
作者：
Van Leenders, GJLH;Beerlage, HP;van de Kaa, CA
通讯作者：
van de Kaa, CA
影响因子：
2.9
作者：
HILL, CR;RIVENS, I;TERHAAR, GR
通讯作者：
TERHAAR, GR
影响因子：
4.4
作者：
Preynat-Seauve, O;Schuler, P;French, LE
通讯作者：
French, LE
影响因子：
7.4
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
通讯作者：
Zhong, Pei