颗粒素+巨细胞通过近信号循环促进前列腺癌的血统可塑性
Zhipeng Zhu1,2,3, Mi Zhang4,5, Ying Song1,2,3
1Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China.
Genomics, proteomics & bioinformatics
|March 16, 2026
概括
颗粒素表达性巨细胞通过促进血统可塑性来驱动前列腺癌治疗耐药性. 抑制CSF1R会破坏这种抗性,为晚期前列腺癌提供一种潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 血统可塑性是前列腺癌治疗耐药性的已知原因之一.
- 瘤透免疫细胞在这种表型切换中的作用尚不清楚.
研究的目的:
- 描述免疫透,转录性变化和前列腺癌进展中的细胞通信.
- 通过血统可塑性识别驱动疗法耐药性的机制.
主要方法:
- 对前列腺癌进展的单细胞多组分析.
- 使用体外模型和患者衍生器官的功能验证.
- 在小鼠模型中进行治疗干预研究 (TRAMP).
主要成果:
- 长质素 (GRN) 表达性巨细胞通过GRN/TNFRSF1A和NF-κB通路促进腺癌转化为耐治疗多系细胞状态.
- 一个涉及CSF1/CSF1R的前循环维持了谱系可塑性.
- GRN驱动上皮层-介质酶过渡和酶胺耐药性.
- 抑制CSF1R可以减少GRN+巨细胞,并抑制多系子克隆的出现.
- 确定了与疾病复发相关的新型 stromal 种群.
结论:
- 在前列腺癌中,GRN+巨细胞是血统可塑性和治疗抵抗性的关键媒介.
- GRN/CSF1R轴代表了一个有前途的治疗标.
- 了解瘤-免疫交叉通话对于克服晚期前列腺癌抗性至关重要.
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