聚焦超声诱导的血脑屏障开放增强肿瘤灌注,为胶质瘤的抗PD-1免疫疗法增效

IF 5 2区 医学 Q2 Medicine
Haiyan Shan , Guangrong Zheng , Shasha Bao , Haiyan Yang , Ujen Duwal Shrestha , Guochen Li , Xirui Duan , Xiaolan Du , Tengfei Ke , Chengde Liao
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引用次数: 0

摘要

目的 证明在胶质瘤大鼠中使用聚焦超声增强 PD-1 抑制剂递送的可行性,并确定这种方法是否能提高疗效。本研究采用 C6 脑胶质瘤原位大鼠模型,用 FUS 结合微气泡进行经颅照射,以打开血脑屏障(BBB)。在正常大鼠身上评估了打开 BBB 的疗效。将患有胶质瘤的大鼠分组,以评估 PD-1 抑制剂结合 FUS 诱导的免疫反应在 BBB 打开时抑制胶质瘤的作用。流式细胞术用于检测大鼠外周血、肿瘤组织和脾脏组织中淋巴细胞等免疫细胞群的变化。大鼠脑组织切片也被用于组织学和免疫组化分析。结果 FUS 联合微气泡可通过增加 BBB 的通透性来增强肿瘤的血液灌注(p <0.0001),从而促进 CD4+ T 淋巴细胞的浸润(p <0.01)。与对照组相比,联合治疗组的CD4+(p < 0.05)和CD8+ T(p < 0.05)浸润数量增加;联合治疗组的肿瘤体积小于对照组(p < 0.结论在这项研究中,我们证明了FUS诱导的BBB瞬时开放增强了肿瘤血管灌注,促进了PD-1抑制剂的递送,最终提高了胶质母细胞瘤的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Tumor perfusion enhancement by focus ultrasound-induced blood-brain barrier opening to potentiate anti-PD-1 immunotherapy of glioma

Objective

To demonstrate the feasibility of using focused ultrasound to enhance delivery of PD-1 inhibitors in glioma rats and determine if such an approach increases treatment efficacy.

Methods

C6 glioma in situ rat model was used in this study. Transcranial irradiation with FUS combined with microbubbles was administered to open the blood-brain barrier (BBB). The efficacy of BBB opening was evaluated in normal rats. The rats with glioma were grouped to evaluate the role of PD-1 inhibitors combined with FUS-induced immune responses in suppressing glioma when the BBB opens. Flow cytometry was used to examine the changes of immune cell populations of lymphocytes in peripheral blood, tumor tissue and spleen tissue of the rats. A section of rat brain tissue was also used for histological and immunohistochemical analysis. The survival of the rats was then monitored; the tumor progression and changes in blood perfusion of tumor were dynamically observed in vivo using multimodal MRI.

Results

FUS combined with microbubbles could enhance the blood perfusion of tumors by increasing the permeability of BBB (p < 0.0001), thus promoting the infiltration of CD4+ T lymphocytes (p < 0.01). Compared with the control group, the combination treatment group had increased in the infiltration number of CD4+(p < 0.05) and CD8+ T (p < 0.05); the tumor volume of the combined treatment group was smaller than that of the control group (p < 0.01) and the survival rate of the rats was prolonged (p < 0.05).

Conclusions

In this study, we demonstrated that the transient opening of the BBB induced by FUS enhanced tumor vascular perfusion and facilitated the delivery of PD-1 inhibitors, ultimately improving the therapeutic efficacy for glioblastoma.

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来源期刊
CiteScore
8.40
自引率
2.00%
发文量
314
审稿时长
54 days
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
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