肺癌进化中的新抗原导向免疫逃逸
Rachel Rosenthal1,2,3, Elizabeth Larose Cadieux4, Roberto Salgado5,6
1Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK.
Nature
|March 22, 2019
概括
免疫微环境塑造了早期肺癌的演变,通过各种机制驱动免疫逃避. 了解这些过程对于预测患者的结果和开发有效的治疗方法至关重要.
科学领域:
- 癌症学
- 免疫学
- 遗传学
背景情况:
- 进化癌症与免疫微环境之间的动态相互作用尚未完全理解.
- 早期未经治疗的非小细胞肺癌 (NSCLC) 是研究这些相互作用的关键窗口.
- 透瘤的淋巴细胞是影响癌症进展的免疫微环境的关键组成部分.
研究的目的:
- 研究早期NSCLC免疫透和瘤演变之间的关系.
- 确定由瘤微环境驱动的免疫逃避机制.
- 确定这些免疫规避策略的临床相关性.
主要方法:
- 分析了88名早期NSCLC患者的258个瘤区域.
- 使用RNA测序和组织病理学进行TIL估计.
- 检查了新抗原呈现,人类白细胞抗原 (HLA) 状态和基因促进物甲基化.
主要成果:
- 免疫透在瘤内和瘤之间有显著差异.
- 不同的免疫微环境与不同的新抗原呈现缺陷有关.
- 免疫规避的机制包括历史免疫编辑,拷贝数量损失,HLA异性损失,新抗原枯竭和通过促进剂高甲基化进行表观遗传沉默.
- 新抗原基因的促进性高甲基化被确定为表观遗传免疫编辑机制.
结论:
- 免疫微环境对早期的NSCLC施加强大的选择压力.
- 通过瘤进化建立了多种免疫逃避途径.
- 这些免疫逃避机制在临床上具有重要意义,并且与无病生存率差相关.
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