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同步微束放射治疗在 EMT6.5 乳腺肿瘤中引起与常规放射治疗不同的早期肿瘤免疫调节反应。

Synchrotron microbeam radiotherapy evokes a different early tumor immunomodulatory response to conventional radiotherapy in EMT6.5 mammary tumors.

机构信息

Department of Obstetrics & Gynaecology, University of Melbourne, Royal Women's Hospital, Parkville, Australia.

MRC Centre for Reproductive Health, Queen's Medical Research Institute, The University of Edinburgh, UK.

出版信息

Radiother Oncol. 2019 Apr;133:93-99. doi: 10.1016/j.radonc.2019.01.006. Epub 2019 Jan 22.

Abstract

BACKGROUND

Synchrotron microbeam radiation therapy (MRT) is a new, evolving form of radiotherapy that has potential for clinical application. Several studies have shown in preclinical models that synchrotron MRT achieves equivalent tumor control to conventional radiotherapy (CRT) but with significantly reduced normal tissue damage.

METHODS

To explore differences between these two modalities, we assessed the immune cell infiltrate into EMT6.5 mammary tumors after CRT and MRT.

RESULTS

CRT induced marked increases in tumor-associated macrophages and neutrophils while there were no increases in these populations following MRT. In contrast, there were higher numbers of T cells in the MRT treated tumors. There were also increased levels of CCL2 by immunohistochemistry in tumors subjected to CRT, but not to MRT. Conversely, we found that MRT induced higher levels of pro-inflammatory genes in tumors than CRT.

CONCLUSION

Our data are the first to demonstrate substantial differences in macrophage, neutrophil and T cell numbers in tumors following MRT versus CRT, providing support for the concept that MRT evokes a different immunomodulatory response in tumors compared to CRT.

摘要

背景

同步辐射微束放射治疗(MRT)是一种新的、不断发展的放射治疗形式,具有临床应用的潜力。一些研究在临床前模型中表明,同步辐射 MRT 实现了与传统放射治疗(CRT)相当的肿瘤控制,但正常组织损伤明显减少。

方法

为了探索这两种方式的差异,我们评估了 CRT 和 MRT 后 EMT6.5 乳腺肿瘤中的免疫细胞浸润。

结果

CRT 诱导肿瘤相关巨噬细胞和中性粒细胞显著增加,而 MRT 后这些细胞群没有增加。相比之下,MRT 治疗的肿瘤中有更多的 T 细胞。CRT 引起的肿瘤中 CCL2 的免疫组化水平也升高,但 MRT 则不然。相反,我们发现 MRT 诱导的肿瘤中促炎基因水平高于 CRT。

结论

我们的数据首次表明,MRT 与 CRT 后肿瘤中巨噬细胞、中性粒细胞和 T 细胞数量存在显著差异,这支持了 MRT 在肿瘤中引发与 CRT 不同的免疫调节反应的概念。

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