Immune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer.
Immune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer.
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在小鼠乳腺癌模型中磁共振引导的高强度聚焦超声所产生的免疫调节
DOI：
10.1038/s41598-020-80135-1
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发表时间：
2021-01-13
影响因子：
4.6
通讯作者：
Ferrara KW
中科院分区：
文献类型：
--
作者：
Fite BZ;Wang J;Kare AJ;Ilovitsh A;Chavez M;Ilovitsh T;Zhang N;Chen W;Robinson E;Zhang H;Kheirolomoom A;Silvestrini MT;Ingham ES;Mahakian LM;Tam SM;Davis RR;Tepper CG;Borowsky AD;Ferrara KW
高强度聚焦超声（HIFU）能快速且无创地破坏肿瘤组织。在此，我们试图评估磁共振引导的HIFU及其与天然免疫激动剂CpG和检查点抑制剂抗PD - 1联合使用的免疫调节效应。患有多灶性乳腺癌的小鼠接受消融治疗，采用一组旨在以最小热剂量实现机械破坏的参数，或者采用一种使肿瘤温度达到65°C的方案。小鼠要么单独接受HIFU治疗，要么用Toll样受体9激动剂CpG和检查点调节剂抗PD - 1进行预处理。与对照组相比，机械性HIFU和热消融均诱导了强烈的炎症反应，Nlrp3、Jun、Mefv、Il6和Il1β的表达增加，巨噬细胞极化发生改变。此外，HIFU上调了多种天然免疫受体和免疫通路，包括Nod1、Nlrp3、Aim2、Ctsb、Tlr1/2/4/7/8/9、Oas2和RhoA。炎症反应大多是无菌的，且与伤口愈合一致。用CpG预处理可减弱Il6和Nlrp3的表达，进一步上调Nod2、Oas2、RhoA、Pycard、Tlr1/2和Il12的表达，增加T细胞数量并增强其活化，同时使巨噬细胞极化为抗肿瘤表型。HIFU释放的肿瘤特异性抗原、细胞因子和细胞碎片增强了对天然免疫激动剂的反应。
High intensity focused ultrasound (HIFU) rapidly and non-invasively destroys tumor tissue. Here, we sought to assess the immunomodulatory effects of MR-guided HIFU and its combination with the innate immune agonist CpG and checkpoint inhibitor anti-PD-1. Mice with multi-focal breast cancer underwent ablation with a parameter set designed to achieve mechanical disruption with minimal thermal dose or a protocol in which tumor temperature reached 65 °C. Mice received either HIFU alone or were primed with the toll-like receptor 9 agonist CpG and the checkpoint modulator anti-PD-1. Both mechanical HIFU and thermal ablation induced a potent inflammatory response with increased expression of Nlrp3, Jun, Mefv, Il6 and Il1β and alterations in macrophage polarization compared to control. Furthermore, HIFU upregulated multiple innate immune receptors and immune pathways, including Nod1, Nlrp3, Aim2, Ctsb, Tlr1/2/4/7/8/9, Oas2, and RhoA. The inflammatory response was largely sterile and consistent with wound-healing. Priming with CpG attenuated Il6 and Nlrp3 expression, further upregulated expression of Nod2, Oas2, RhoA, Pycard, Tlr1/2 and Il12, and enhanced T-cell number and activation while polarizing macrophages to an anti-tumor phenotype. The tumor-specific antigen, cytokines and cell debris liberated by HIFU enhance response to innate immune agonists.
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影响因子：
3.3
作者：
Gaur, Pooja;Grissom, William A.
通讯作者：
Grissom, William A.
DOI：
10.1038/nri2851
发表时间：
2010-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.3
作者：
Andrade, F;Casciola-Rosen, L;Rosen, A
通讯作者：
Rosen, A
影响因子：
8.7
作者：
Dinarello CA
通讯作者：
Dinarello CA
影响因子：
15.9
作者：
Huber, Veronica;Vallacchi, Viviana;Rivoltini, Licia
通讯作者：
Rivoltini, Licia