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痕信号抑制神经内分泌的分化,并改变了晚期前列腺癌的免疫微环境
Sheng-Yu Ku1, Yanqing Wang2, Maria Mica Garcia1
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
The Journal of clinical investigation
|July 18, 2024
概括
痕信号抑制神经内分泌前列腺癌的进展. 在晚期前列腺癌模型中激活Notch反转了神经内分泌表型,促进了更少的攻击性状态并增强了抗瘤免疫力.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 痕信号在癌症中表现出取决于背景的作用,作为瘤原体或瘤抑制剂.
- 在早期前列腺癌中,Notch信号可能是致癌的,但其在晚期,特别是神经内分泌前列腺癌 (NEPC) 中的作用不明.
研究的目的:
- 调查Notch信号在晚期前列腺癌中的功能,特别是其在过渡到神经内分泌前列腺癌 (NEPC) 中的作用.
- 确定Notch路径激活是否可以逆转NEPC表型并影响瘤微环境 (TME).
主要方法:
- 在前列腺癌从腺癌到NEPC的进展过程中,分析Notch通路的表达.
- 在NEPC (Rb1/Trp53缺乏) 的临床前模型中激活Notch信号.
- 在Notch激活后评估表型变化,血统标记表达和免疫细胞透.
主要成果:
- 在前列腺癌进展到NEPC期间,切口路径显著下调.
- 在NEPC模型中激活Notch信号诱导了表型转换到一个更惰的非NE状态,具有腺体特征.
- 口激活导致光线标记物的表达增加,MHC和I型IFN的上调,并增强了免疫细胞的透.
结论:
- 在先进的NEPC中,痕信号作为瘤抑制剂,抑制神经内分泌分化.
- 口路径激活可以逆转侵略性的NEPC表型,并将TME重塑为抗瘤免疫反应.
- 这些发现突显了Notch信号在血统可塑性中的作用,并为NEPC提供了潜在的治疗策略.
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