针对CXCL12的免疫调节基因治疗减少了健康组织中辐射诱导的纤维化
James T Paget1, Joseph A Ward1, Andrew R McKean1
1Chester Beatty Laboratories, Targeted Therapy Team, The Institute of Cancer Research, London, United Kingdom.
Molecular cancer therapeutics
|December 12, 2024
概括
调节CXCL12信号通过减少巨细胞的招募来减少辐射诱导的纤维化. 针对CXCL12/osteopontin轴可以增强抗瘤免疫力,减少纤维化.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 纤维化研究 纤维化研究
背景情况:
- 辐射诱导纤维化 (RIF) 是影响癌症幸存者的重大并发症.
- CXCL12是一种参与纤维化过程的免疫瘤因子.
研究的目的:
- 调查CXCL12在RIF中的作用.
- 为了确定调节CXCL12是否可以减轻RIF并影响抗瘤反应.
主要方法:
- 在动物RIF模型中特征CXCL12表达.
- 使用的lentiviral载体使其沉默 (LVShCXCL12) 或过度表达 (LVOeCXCL12) CXCL12.
- 量化了纤维化结果,进行了流细胞计,谱系追踪和RNA测序.
- 在具有调节CXCL12水平的组织中对放射治疗 (RT) 的评估瘤反应.
主要成果:
- 照射纤维细胞中的CXCL12上调与CD68+巨细胞招募相关.
- 沉默CXCL12减少了RIF和巨细胞的透.
- 转录组分析发现骨质素 (OPN) 具有差异表达.
- 减少CXCL12和OPN表达减少了周纤维化,增强了CD8+T细胞透和抗瘤反应.
- OPN阻塞改善了内CD8+T细胞激活,并减缓了瘤的生长.
结论:
- CXCL12/OPN轴对于纤维化发育中的免疫-流体交叉至关重要.
- 该轴的治疗向具有减少RIF和提高抗瘤功效的潜力.
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