瘤微环境中的细胞动态与肺癌进展一起强调了中性粒细胞的空间和进化异质性
Haoxin Peng1,2,3, Xiangrong Wu1,2,4, Shaopeng Liu5,6
1Department of Thoracic Oncology and Surgery, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Clinical and translational medicine
|July 26, 2023
概括
在非小细胞肺癌 (NSCLC) 中发现了瘤微环境动态. 与瘤相关的中性粒细胞 (TAN) 呈现出多种亚型和作用,影响预后和免疫治疗反应.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 计算生物学 计算生物学
背景情况:
- 在非小细胞肺癌 (NSCLC) 进展过程中,瘤微环境 (TME) 内的细胞动态尚未完全理解.
- 研究TME内部复杂的相互作用对于开发有效的癌症疗法至关重要.
研究的目的:
- 阐明NSCLC中TME的细胞组成,空间组织和功能重编程.
- 描述瘤相关中性粒细胞 (TAN) 在NSCLC进展中的异质性和免疫调节作用.
主要方法:
- 在553个NSCLC原发性瘤 (PT) 样本上对10个免疫标记物的多重免疫光染色.
- 使用StarDist深度学习模型对TME进行空间分析.
- 单细胞转录组分析PT和结合的瘤排水淋巴结 (TDLNs).
- 使用公共数据库进行生物信息学分析 (GEO,TCGA,Array-Express).
主要成果:
- 观察到NSCLC进展时免疫细胞 (例如T细胞,中性粒细胞,巨细胞) 的空间分布发生变化.
- 中性粒细胞显示阶段和位置依赖的预后效应,影响生存.
- 在PT和TDLN微环境中发现了显著的分子和功能重编程.
- 确定了五种不同的TAN亚型,具有不同的功能,包括抗原呈现,IFN刺激,亲瘤原生,经典和亲炎症作用.
- 开发了一种预测患者风险和潜在免疫治疗反应的六基因模型.
结论:
- 解读了NSCLC TME和TDLNs在瘤进展过程中的细胞和分子变化.
- 突出了TANs在NSCLC中的显著免疫调节作用和进化异质性.
- 建立了基于中性粒细胞相关基因的患者预后和免疫治疗反应的预测模型.
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