在转移性乳腺癌中,p38阻塞逆转了免疫抑制性瘤微环境
bioRxiv : the preprint server for biology
|July 14, 2025
概括
在转移性乳腺癌 (MBC) 中阻断p38α通过增强CD8+T细胞活性和抑制髓质衍生抑制细胞来减少转移. 这一发现为改善抗瘤免疫力和MBC患者的治疗结果提供了新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 转移性乳腺癌 (MBC) 由于免疫抑制性瘤微环境 (TME),具有有限的治疗选择.
- 这种TME阻碍了有效的抗瘤免疫反应,促进了疾病的进展和转移.
研究的目的:
- 调查p38α作为TME中的可药物标.
- 阐明p38α在调节免疫-瘤相互作用和转移中的作用.
主要方法:
- 通过CRISPR/Cas9.9对p38α的系统性阻断和瘤特异性的p38α失活.
- 免疫-TME的单细胞转录组分析.
- 免疫类型定型,体外增殖试验和骨髓菌群体体内体内分析.
主要成果:
- p38α阻断减少了转移,这种影响取决于CD8+ T细胞.
- 抑制p38α导致较少耗尽,更活跃的CD8+T细胞表型,抑制受体 (PD-1,LAG-3,CTLA-4) 的表达减少.
- p38阻塞主要影响髓状细胞群 (MDSCs,TAMs) 和减少前转移性细胞因子/化学因子表达.
结论:
- p38α驱动一种免疫抑制的TME,并促进转移.
- 治疗阻断p38α增强抗瘤免疫力,对改善MBC患者的治疗结果有重大影响.
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