UNASSIGNED:研究MVX射线超高剂量率放疗(FLASH-RT)和常规剂量率放疗(CONV-RT)后乳腺癌小鼠的抗肿瘤作用和肿瘤内以及局部免疫反应。
UNASSIGNED:6周龄雌性C57BL/6小鼠在腹股沟乳腺皮下接种Py8119和Py230乳腺肿瘤细胞,并在肿瘤接种15天后给予10Gy腹部6MVX线FLASH-RT(125Gy/s)或CONV-RT(0.2Gy/s)。在照射后(PI)的不同时间点获得肿瘤和脾组织,用于使用流式细胞术和免疫组织化学(IHC)染色分析免疫细胞浸润。收集3天的肠道组织PI评价正常组织损伤和免疫细胞浸润。
未经批准:FLASH-RT和CONV-RT均显著延迟肿瘤生长。流式细胞术显示CD8+/CD3+和CD8+/CD4+比值增加,和IHC证实在两个照射组中的Py8119肿瘤组织中在2周PI时CD8+T细胞浸润相似增加。在肿瘤生长和肿瘤中T细胞浸润增加方面,辐照组之间未观察到统计学差异。出乎意料的是,与未照射的对照组和CONV-RT组4周PI相比,在FLASH-RT组的脾脏中观察到明显更小的脾脏重量和更高的CD8+/CD3+和更低的CD4+/CD3+比率。病理分析显示CONV-RT组的几个脾脏中严重的红髓扩张,但不在FLASH-RT组的脾脏中。减少肠道损伤,FLASH-RT组与CONV-RT组比较,观察到巨噬细胞和中性粒细胞浸润。
未经证实:FLASH-RT和CONV-RT可有效抑制肿瘤生长并促进CD8+T细胞流入肿瘤。FLASH-RT能诱导不同的脾免疫反应,减轻辐射对脾脏和肠道的损伤,这可能潜在地提高FLASH-RT的治疗比例。
UNASSIGNED: Investigating the antitumor effect and intratumor as well as local immune response in breast cancer-bearing mice after MV X-ray ultra-high dose rate radiotherapy (FLASH-RT) and conventional dose rate radiotherapy (CONV-RT).
UNASSIGNED: Six-week-old female C57BL/6 mice were inoculated subcutaneously with Py8119 and Py230 breast tumor cells in the inguinal mammary gland and administered 10 Gy abdominal 6 MV X-ray FLASH-RT (125 Gy/s) or CONV-RT (0.2 Gy/s) 15 days after tumor inoculation. Tumor and spleen tissues were obtained at different time points post-irradiation (PI) for analysis of immune cell infiltration using flow cytometry and immunohistochemical (IHC) staining. Intestine tissues were collected 3 days PI to evaluate normal tissue damage and immune cell infiltration.
UNASSIGNED: Both FLASH-RT and CONV-RT significantly delayed tumor growth. Flow cytometry showed increased CD8+/CD3 + and CD8+/CD4 + ratios, and IHC confirmed a similar increased CD8 + T cell infiltration at 2 weeks PI in Py8119 tumor tissues in both irradiation groups. No statistical difference was observed between the irradiation groups in terms of tumor growth and increased T cell infiltration in the tumor. Unexpectedly, significantly smaller spleen weight and substantially higher CD8+/CD3 + and lower CD4+/CD3 + ratios were observed in the spleens of the FLASH-RT group than in the spleens of the non-irradiated control and CONV-RT groups 4 weeks PI. Pathological analysis revealed severe red pulp expansion in several spleens from the CONV-RT group, but not in the spleens of the FLASH-RT group. Reduced intestinal damage, macrophage and neutrophil infiltration were observed in the FLASH-RT group compared with CONV-RT group.
UNASSIGNED: FLASH-RT and CONV-RT effectively suppressed tumor growth and promoted CD8 + T cell influx into tumors. FLASH-RT can induce different splenic immune responses and reduce radiation-induced damage in the spleen and intestine, which may potentially enhance the therapeutic ratio of FLASH-RT.