表观遗传疗法通过破坏转移前的位来抑制转移
Zhihao Lu1,2,3, Jianling Zou2, Shuang Li2
1Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nature
|February 28, 2020
概括
低剂量表观遗传疗法通过向形成转移前微环境的髓状细胞 (MDSC) 来预防癌症复发. 这种方法抑制了转移的形成和生长,改善了初级瘤切除后的存活率.
科学领域:
- 癌症学
- 免疫学
- 表观遗传学
背景情况:
- 手术后癌症复发是一个重大的临床挑战.
- 骨髓衍生抑制细胞 (MDSCs) 创建先转移的微环境,帮助远程瘤扩散.
- 目前缺乏预防前转移性位形成的干预措施.
研究的目的:
- 研究低剂量辅助表观遗传疗法在预防癌症复发方面的有效性.
- 确定MDSC在初级瘤切除后的前转移性位形成中的作用.
- 探索表观遗传疗法影响MDSC和转移的机制.
主要方法:
- 在初级瘤切除后使用肺转移的小鼠模型.
- 使用低剂量的辅助表观遗传疗法,使用5-阿扎丁和氨酸.
- 分析了MDSC在转移前的肺部中的流通,分化和积累.
- 与化疗相比,评估了对无疾病和整体存活率的影响.
主要成果:
- 在肺癌,乳腺癌和食道癌模型中,低剂量表观遗传疗法有效地破坏了转移前的微环境.
- 治疗选择性地向MDSC,通过CCR2和CXCR2降低调节抑制它们的贩运.
- 促进了MDSC向间位性巨类表型的分化.
- 在转移前的肺部减少MDSC积累导致了更好的生存结果.
结论:
- 即使在初级瘤切除后,MDSC对于前转移的发展和残留瘤细胞的沉积至关重要.
- 低剂量辅助表观遗传疗法提供了一种新的策略来破坏前转移的微环境并抑制转移.
- 这种方法有助于改善癌症患者的生存率.
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