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在小细胞肺癌中由肺纤维细胞诱导的动态表型重编程和化学抵抗

Yuanhua Lu¹, Hui Li², Peiyan Zhao²

¹Postdoctoral Research Workstation, Jilin Cancer Hospital, Changchun, China.

Scientific reports

|February 4, 2024

概括

与癌症相关的纤维细胞 (CAF) 驱使小细胞肺癌 (SCLC) 细胞从神经内分泌变化为非神经内分泌的表型. 这种重编程促进了炎症瘤微环境和SCLC中的化学抵抗.

科学领域:

在瘤学瘤学.
癌症生物学癌症生物学
瘤微环境瘤微环境

背景情况:

小细胞肺癌 (SCLC) 的特点是表型异质性,重编程机制不明.
癌症相关纤维细胞 (CAFs) 参与癌症进展,但它们在SCLC表型可塑性中的作用尚不清楚.

研究的目的:

研究CAFs在SCLC表型重编程中的作用.
阐明CAFs影响SCLC特征的分子机制.
探索CAF介导的重编程对瘤免疫微环境和化学抵抗的影响.

主要方法:

从SCLC组织中分析公开的转录组数据.
估计CAF的丰度和与SCLC表型的相关性.
肺纤维细胞和SCLC细胞的体外共同培养系统.
评估包括JAK2/STAT3,c-MYC和NOTCH在内的信号通路.
评估免疫细胞透和化学抵抗.

主要成果:

富含CAF的SCLC表现出非神经内分泌 (非NE) 的特征.
纤维细胞诱导SCLC细胞通过IL-6/JAK2/STAT3/c-MYC/NOTCH信号从NE转变为非NE表型.
富含CAF的SCLC显示免疫细胞透率增加和免疫激活特征的高表达.
纤维细胞赋予SCLC细胞的化学抵抗,这种抵抗在JAK抑制剂下是可逆的.

结论:

纤维细胞诱导SCLC的表型重编程从NE到非NE.
这种重编程导致SCLC炎症的免疫微环境和化学抵抗.
CAFs代表了调节SCLC表型和克服治疗耐药性的潜在治疗标.

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