基底向炎症转变和瘤耐药性通过交叉与一个亲炎症的 stromal 利基的交叉
Nancy Yanzhe Li1, Weiruo Zhang2, Daniel Haensel1
1Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Nature communications
|September 17, 2024
概括
炎症驱动一种新的抗药性瘤状态,即基本到炎症的过渡,影响患者的生存. 这种与TREM1髓状细胞相关的过渡,在上皮癌中提供了潜在的治疗点.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 与癌症相关的炎症具有复杂的亲和抗瘤作用,这是由于人们对瘤与免疫相互作用的理解不足所致.
- 一个先前确定的抗药性途径,基底细胞癌转移到状细胞癌,在瘤内本质上发生.
研究的目的:
- 识别和描述一种新的炎症和治疗丰富的瘤状态.
- 研究瘤微环境在驱动治疗耐药性的作用.
主要方法:
- 采用了多方单细胞和空间-omics方法.
- 分析了与瘤相关的TREM1髓质细胞特征及其分泌的细胞因子 (IL1,OSM).
- 研究了NF-κB信号通路的作用.
- 评估了患者的基础细胞癌扩散瘤对Smoothened抑制剂治疗的敏感性.
主要成果:
- 鉴定了一种'基底向炎症过渡'瘤状态,与表皮瘤中患者存活率差相关.
- 这种过渡发生在与瘤核心区分开的区域,其特点是具有特定的炎症微环境和TREM1骨髓体特征.
- 通过NF-κB诱导TREM1骨髓衍生的细胞因子IL1和OSM,通过NF-κB诱导基底向炎症过渡,降低对Smoothened抑制剂的敏感性.
结论:
- 基础到炎症的过渡代表了由专门的炎症微环境驱动的耐药瘤状态.
- 这一发现加深了对瘤微环境异质性的理解.
- 从基底到炎症的过渡被提名为潜在的治疗点.
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