将两次分集性消融放射治疗间隔为五天,有助于增强抗肿瘤免疫力。
Five-day Spacing of Two Fractionated Ablative Radiotherapies Enhances Anti-Tumor Immunity.
发表日期:2023 Sep 15
作者:
Hyunkyung Kim, Eunju Lee, Haeun Cho, Eunji Kim, Won Il Jang, Kwangmo Yang, Yoon-Jin Lee, Tae-Jin Kim, Mi-Sook Kim
来源:
Int J Radiat Oncol
摘要:
本研究旨在通过应用不同的立体定向消融全身放射治疗(SABR)方案来增强肿瘤控制和阿布斯科平效应。使用FSaII、CT-26和4T1细胞进行一天或五天间隔辐射治疗(RT)后的肿瘤生长延迟和肺转移分析,剂量分别为40、20和20 Gy。使用免疫缺陷的BALB/c裸鼠、免疫能力正常的C3H小鼠和BALB/c小鼠模型。对于免疫监测,使用流式细胞术、免疫荧光染色和qRT-PCR分析FSaII肿瘤。脾脏用于ELISpot检测和流式细胞术以确定效应T细胞。对于CT-26肿瘤的阿布斯科效应分析,分别在一天和五天间隔辐照主要肿瘤后测量非辐照次要肿瘤的体积。与高剂量一天间隔RT相反,五天间隔的RT在免疫能力正常的小鼠中显著延缓了肿瘤生长,而在免疫缺陷小鼠中未观察到这种现象。此外,五天间隔RT显著减少了FSaII和CT-26肿瘤的肺转移数量。五天间隔比一天间隔更有效地增强了抗肿瘤免疫,通过增加肿瘤特异性IFN-γ的分泌,激活CD8 T细胞并抑制单核嗜髓样抑制细胞(M-MDSCs)。与一天间隔相比,五天间隔更有效地抑制了非辐照次要肿瘤的生长。与一天间隔RT相比,五天间隔RT方案显示了与M-MDSCs抑制相关的CD8 T细胞的增强抗肿瘤免疫。增强抗肿瘤免疫导致了初级肿瘤控制和阿布斯科效应的显著改善。版权所有© 2023。由Elsevier Inc.发表。
This study aimed to enhance tumor control and abscopal effects by applying diverse stereotactic ablative body radiation (SABR) schedules.FSaII, CT-26, and 4T1 cells were used for tumor growth delay and lung metastases analysis after one- or five-day interval radiotherapy (RT) with 40, 20, and 20 Gy, respectively. Immunodeficient BALB/c-nude, immunocompetent C3H, and BALB/c mouse models were used. For immune monitoring, FSaII tumors were analyzed using flow cytometry, immunofluorescence staining, and qRT-PCR. The spleens were used for the ELISpot assay and flow cytometry to determine effector CD8 T-cells. For abscopal effect analysis in CT-26 tumors, the volume of the non-irradiated secondary tumors was measured after primary tumors were irradiated with one-day or five-day interval, respectively.Contrary to the high-dose one-day interval RT, the five-day interval RT significantly delayed tumor growth in immunocompetent mice, which was not observed in immunodeficient mice. In addition, the five-day interval RT significantly reduced the number of lung metastases in FSaII and CT-26 tumors. Five-day spacing was more effective than one-day interval in enhancing the anti-tumor immunity via increasing the secretion of tumor-specific IFN-γ, activating the CD8 T-cells, and suppressing the monocytic myeloid-derived suppressor cells (M-MDSCs). The five-day spacing inhibited non-irradiated secondary tumor growth more effectively than did the one-day interval.Compared to the one-day interval RT, the five-day interval RT scheme demonstrated enhanced anti-tumor immunity of CD8 T-cells associated with inhibition of M-MDSCs. Enhancing anti-tumor immunity led to significant improvements in both primary tumor control and the abscopal effect.Copyright © 2023. Published by Elsevier Inc.