An Antitumor Immune Response Is Evoked by Partial-Volume Single-Dose Radiation in 2 Murine Models.
An Antitumor Immune Response Is Evoked by Partial-Volume Single-Dose Radiation in 2 Murine Models.
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DOI：
10.1016/j.ijrobp.2018.10.009
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发表时间：
2019-03-01
期刊：
影响因子：
--
通讯作者：
Haimovitz-Friedman A
中科院分区：
文献类型：
--
作者：
Markovsky E;Budhu S;Samstein RM;Li H;Russell J;Zhang Z;Drill E;Bodden C;Chen Q;Powell SN;Merghoub T;Wolchok JD;Humm J;Deasy JO;Haimovitz-Friedman A
目的：研究部分照射对临床前小鼠肿瘤生长的延迟作用。我们研究了免疫活性小鼠和裸鼠的67NR小鼠原位乳腺肿瘤。使用微型辐射器上的2×2 cm准直器对50%或100%的肿瘤进行治疗。用抗CD8和抗ICAM抗体调节放射反应。使用免疫原性较低的Lewis肺癌(LLC)小鼠模型进行了类似的实验。于放疗后1天和7天检测肿瘤生长延迟和g-γH_2AX磷酸化，免疫荧光和流式细胞仪检测免疫反应。在放疗后不同时间检测肿瘤细胞黏附分子的表达。在免疫能力强的小鼠身上，部分照射导致的肿瘤反应与完全暴露的肿瘤相似，但在裸鼠身上则不然。单次照射10Gy后，可见CD8+T细胞浸润，ICAM表达增加。抗CD8抗体或抗ICAM抗体均可消除肿瘤对10Gy射线照射的反应。在免疫原性较低的LLC小鼠模型中也得到了类似的反应，将15Gy射线照射到肿瘤体积的一半。FTY720是一种抑制T细胞从淋巴结输出的化合物，当CD8+T细胞在肿瘤的非照射区域渗入时，FTY720治疗并没有影响肿瘤的反应，这表明这些细胞最有可能的来源是半照射肿瘤的照射部分。此外，在67NR模型中，单次照射10Gy后，观察到明显的非局域效应。在这些模型中，辐射通过直接杀死细胞和间接通过免疫激活来控制肿瘤的生长。这增加了在临床上诱导这种效应的可能性。
To study tumor growth delay resulting from partial irradiation in preclinical mouse models. We investigated 67NR murine orthotopic breast tumors in both immunocompetent and nude mice. Treatment was delivered to 50% or 100% of the tumor using a 2×2 cm collimator on a micro-irradiator. Radiation response was modulated by treating with anti-CD8 and anti-ICAM antibodies. Similar experiments were performed using the less immunogenic Lewis Lung Carcinoma (LLC) mouse model. Tumor growth delay and gγH2AX phosphorylation were measured and immune response was assessed by immunofluorescence and flow cytometry at 1 and 7 days post-radiotherapy (RT). Tumor expression of cellular adhesion molecules was also measured at different times post-RT. Partial irradiation led to tumor responses similar to fully exposed tumors in immunocompetent mice, but not in nude mice. After a single dose of 10Gy, infiltration of CD8+ T cells was observed, along with increased expression of ICAM. The response to 10Gy in hemi-irradiated tumors was abrogated by treatment with either anti-CD8 or anti-ICAM antibodies. Similar responses were obtained in the less immunogenic LLC mouse model delivering 15Gy to half the tumor volume. Treatment with FTY720, a compound that inhibits T cell egress from lymph nodes, did not affect tumor response at the time of CD8+ T cells infiltration in the non-irradiated area of the tumor, indicating that the most likely source of these cells is the irradiated portion of the hemi-irradiated tumors. In addition, a significant abscopal effect was observed after partial irradiation with a single dose of 10Gy in the 67NR model. In these models, radiation controls tumor growth both directly through cell killing and indirectly through immune activation. This raises the possibility that this effect could be induced in the clinic.
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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：
3.3
作者：
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通讯作者：
Yamada, Yoshiya
影响因子：
3.5
作者：
Golden, Encouse B.;Apetoh, Lionel
通讯作者：
Apetoh, Lionel
影响因子：
20.3
作者：
Lee, Youjin;Auh, Sogyong L.;Fu, Yang-Xin
通讯作者：
Fu, Yang-Xin
DOI：
10.1016/j.ijrobp.2014.03.012
发表时间：
2014-07-01
影响因子：
7
作者：
Kim, D. W. Nathan;Cho, L. Chinsoo;Timmerman, Robert D.
通讯作者：
Timmerman, Robert D.