Immune-Mediated Effects of Microplanar Radiotherapy with a Small Animal Irradiator.
Immune-Mediated Effects of Microplanar Radiotherapy with a Small Animal Irradiator.
复制标题
DOI：
10.3390/cancers14010155
复制
发表时间：
2021-12-29
期刊：
影响因子：
5.2
通讯作者：
Lee YZ
中科院分区：
文献类型：
--
作者：
Bazyar S;O'Brien ET 3rd;Benefield T;Roberts VR;Kumar RJ;Gupta GP;Zhou O;Lee YZ
一半的癌症患者在治疗过程中接受了放射治疗。辐射对正常组织的破坏性影响会产生副作用，严重影响患者的生活质量。微平面放射治疗（MRT）是一种新颖的、有前途的方法，在动物模型中显示出对正常组织的影响较小，治疗效果较好。MRT不会将整个组织暴露在强烈的辐射中，但在辐射峰值之间有微米级的“谷”。我们之前已经开发了一种易于使用的MRT方法。使用我们的方法，在这里，我们表明MRT通过刺激特定的信号分子极大地增强了免疫系统对肿瘤的反应。此外，我们表明MRT与免疫检查点治疗相结合在减少治疗肿瘤方面更有效，可能指向在临床中使用类似的方法。空间分割放疗已被证明对免疫系统有不同于传统放疗（CRT）的影响。我们比较了几个方面的免疫反应CRT相对于空间分割放疗（RT）模型，称为微平面放疗（MRT）。MRT以亚毫米光束（峰值）提供数百个灰色的辐射，由非辐射体积（谷）分开。我们已经开发了一种临床前方法，通过商业小动物辐照器应用MRT。利用B16-F10小鼠黑色素瘤模型，我们首先评估了MRT的体外和体内效果，与CRT相比，MRT具有显著的治疗优势。有趣的是，当MRT应用于Rag - / -和cd8缺失小鼠时，我们观察到治疗反应不显著。免疫组织学分析显示，MRT招募细胞毒性淋巴细胞（CD8），同时抑制调节性T细胞（Tregs）的数量。使用RT-qPCR，我们观察到，与CRT相比，MRT，在我们施加的剂量范围内，显着增加但不饱和CXCL9表达，CXCL9是一种细胞因子，在激活T细胞的吸引中起着至关重要的作用。最后，MRT联合抗ctla -4使一半的病例肿瘤消融，并诱导了长期的全身抗肿瘤免疫。
Half of all cancer patients receive radiation therapy during their course of treatment. The destructive effects of radiation on normal tissue causes side effects that significantly affect the patient’s quality of life. Microplanar radiation therapy (MRT) is a novel, promising method that, in animal models, has shown fewer effects on normal tissue and better therapeutic efficacy. MRT does not expose the entire tissue to intense radiation, but has micron-scale “valleys” between the peaks of radiation. We have previously developed an accessible method to apply MRT. Using our approach, here, we show that MRT greatly enhanced the response of the immune system to the tumor by stimulating specific signaling molecules. Moreover, we show that combining MRT with immune checkpoint therapy was even more effective in reducing the treated tumors, possibly pointing towards using similar approaches in the clinic. Spatially fractionated radiotherapy has been shown to have effects on the immune system that differ from conventional radiotherapy (CRT). We compared several aspects of the immune response to CRT relative to a model of spatially fractionated radiotherapy (RT), termed microplanar radiotherapy (MRT). MRT delivers hundreds of grays of radiation in submillimeter beams (peak), separated by non-radiated volumes (valley). We have developed a preclinical method to apply MRT by a commercial small animal irradiator. Using a B16-F10 murine melanoma model, we first evaluated the in vitro and in vivo effect of MRT, which demonstrated significant treatment superiority relative to CRT. Interestingly, we observed insignificant treatment responses when MRT was applied to Rag−/− and CD8-depleted mice. An immuno-histological analysis showed that MRT recruited cytotoxic lymphocytes (CD8), while suppressing the number of regulatory T cells (Tregs). Using RT-qPCR, we observed that, compared to CRT, MRT, up to the dose that we applied, significantly increased and did not saturate CXCL9 expression, a cytokine that plays a crucial role in the attraction of activated T cells. Finally, MRT combined with anti-CTLA-4 ablated the tumor in half of the cases, and induced prolonged systemic antitumor immunity.
登录
查看更多内容
DOI：
10.1158/1078-0432.ccr-09-0265
发表时间：
2009-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dewan MZ;Galloway AE;Kawashima N;Dewyngaert JK;Babb JS;Formenti SC;Demaria S
通讯作者：
Demaria S
影响因子：
6.4
作者：
Bouchet, Audrey;Sakakini, Nathalie;Pelletier, Laurent
通讯作者：
Pelletier, Laurent
DOI：
10.4049/jimmunol.0903009
发表时间：
2010-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
DiLillo DJ;Yanaba K;Tedder TF
通讯作者：
Tedder TF
影响因子：
5.8
作者：
Lim, Joanne Y. H.;Gerber, Scott A.;Murphy, Shawn P.;Lord, Edith M.
通讯作者：
Lord, Edith M.
影响因子：
3.5
作者：
Bazyar, Soha;Inscoe, Christina R.;Lee, Yueh Z.
通讯作者：
Lee, Yueh Z.