抑制CBP/P300 BRD可降低中性粒细胞的积累,并激活TNBC中的抗瘤免疫力

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Updated: May 3, 2026

Isolation and Characterization of Neutrophils with Anti-Tumor Properties

Isolation and Characterization of Neutrophils with Anti-Tumor Properties

Published on: June 19, 2015

Xueying Yuan¹, Xiaoxin Hao², Hilda L Chan²

¹Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.

bioRxiv : the preprint server for biology

|May 7, 2024

概括

一种针对CREB结合蛋白 (CBP) /P300原蛋白 (BRD) 的新型药物减少了三阴性乳腺癌 (TNBC) 中的促进瘤的中性粒细胞. 这种抑制也增强了抗瘤免疫力,改善了治疗反应.

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:

与瘤相关的中性粒细胞 (TAN) 促进免疫抑制和三阴性乳腺癌 (TNBC) 的进展,与预后不佳相关.
不调节CREB结合蛋白 (CBP) /P300,特别是其原蛋白 (BRD),与各种癌症有关.

研究的目的:

为了研究新型CBP/P300 BRD抑制剂IACS-70654的治疗潜力,在中性粒细胞丰富的TNBC模型中.
阐明CBP/P300 BRD抑制影响TAN,免疫反应和瘤生长的机制.

主要方法:

使用IACS-70654,一个选择性的CBP/P300 BRD抑制剂,在中性粒细胞丰富TNBC的临床前模型中.
评估了CBP/P300 BRD抑制对中性粒细胞原体分化和骨髓中的扩散的影响.
评估瘤细胞免疫反应的变化,包括IFN反应和MHCI表达,以及瘤透的CTLs.

主要成果:

IACS-70654治疗减少了中性粒细胞丰富的TNBC模型中的TAN和抑制瘤生长.
抑制CBP/P300 BRD降低了异常中性粒细胞原体的发育和扩散.
抑制刺激了抗瘤免疫力,由增加的IFN反应,MHCI表达和CTL透证明.
在TNBC模型中,IACS-70654增强了多塞塔克塞尔和免疫检查点阻塞的疗效.

结论:

用IACS-70654针对CBP/P300 BRD是一个有前途的策略,用于管理中性粒细胞丰富的TNBC.
这种方法通过减少TAN和增强抗瘤免疫力来调节瘤微环境.
将CBP/P300 BRD抑制剂与标准疗法相结合,值得在TNBC的未来临床试验中进行调查.

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