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Enhanced antitumor efficacy through microwave ablation combined with a dendritic cell-derived exosome vaccine in hepatocellular carcinoma
International Journal of Hyperthermia ( IF 3.0 ) Pub Date : 2020-10-26 , DOI: 10.1080/02656736.2020.1836406
Xinyu Zhong 1 , Yan Zhou 2, 3 , Yuting Cao 1 , Jianmin Ding 2, 3 , Peng Wang 3 , Ying Luo 3 , Hui Liu 3 , Zhengyan Zhu 3 , Xiang Jing 2, 3
Affiliation  

Abstract

Aim

To investigate the antitumor efficacy of microwave ablation combined with dendritic cell-derived exosomes (Dex) or dendritic cells (DC) in treating hepatocellular carcinoma using a tumor-bearing mouse model.

Methods

We used a bilateral tumor-bearing mouse model treated with MWA, MWA + DC (DC-combined group) or MWA + Dex (Dex-combined group). Following tumor ablation on one side, the tumor volume on the contralateral side was monitored. The proportions of CD8+ (cytotoxic) T cells and regulatory T (Treg) cells in the spleen were analyzed by flow cytometry, and the number of CD8+ T cells and Treg cells in tumor sites was detected by immunohistochemistry. The concentration of interleukin-10 and interferon-γ in plasma was identified using enzyme-linked immunosorbent assay.

Results

The combination therapy significantly inhibited tumor growth compared with MWA monotherapy. In addition, the tumor immune microenvironment was significantly improved in HCC mice in the combination therapy groups compared to MWA group demonstrated by an increased number of CD8+ T cells and a decreased number of Treg cells in tumor sites. A lower proportion of Treg cells were observed in the spleen in the combination therapy groups compared to MWA group. Moreover, the concentration of plasma IFN-γ increased, and the concentration of plasma IL-10 decreased in the combination therapy groups compared to the MWA group. However, there was no statistical difference between the Dex-combined group and the DC-combined group in the comparisons mentioned above.

Conclusions

Our results provide evidence that MWA combined with Dex can significantly inhibit tumor growth and improve the immune microenvironment compared to MWA alone. Furthermore, the immune-enhancing effect of Dex and DC was equivalent in our combination therapy strategy.



中文翻译:

微波消融联合树突状细胞衍生的外来体疫苗增强肝癌的抗肿瘤功效

摘要

目标

为了研究微波消融与树突细胞衍生的外来体(地塞米松),或在使用肿瘤治疗肝细胞癌的树突状细胞(DC)结合的抗肿瘤功效-轴承小鼠模型。

方法

我们使用了双边肿瘤-与MWA,MWA + DC(DC-组合组)或MWA +地塞米松(DEX-联合组)治疗的轴承小鼠模型。一侧的肿瘤消融后,监测对侧的肿瘤体积。用流式细胞仪分析脾脏中CD8 +(细胞毒性)T细胞和调节性T(Treg)细胞的比例,并通过免疫组织化学方法检测肿瘤部位CD8 + T细胞和Treg细胞的数量。使用酶联免疫吸附试验确定血浆中白细胞介素10和干扰素-γ的浓度。

结果

与MWA单一疗法相比,联合疗法显着抑制了肿瘤的生长。另外,与MWA组相比,联合治疗组的HCC小鼠中的肿瘤免疫微环境显着改善,这通过肿瘤部位中CD8 + T细胞数量的增加和Treg细胞数量的减少证明。与MWA组相比,联合治疗组的脾脏中Treg细胞比例较低。而且,与MWA组相比,联合治疗组中血浆IFN-γ的浓度增加,而血浆IL-10的浓度降低。但是,在上述比较中,Dex合并组和DC合并组之间没有统计学差异。

结论

我们的结果提供了证据,与单用MWA相比,MWA与Dex联合使用可显着抑制肿瘤生长并改善免疫微环境。此外,在我们的联合治疗策略中,Dex和DC的免疫增强作用相当。

更新日期:2020-10-30
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