阻断Fas/FasL通路对乳腺癌瘤微环境中的细胞亡和干性的影响 (临床前研究)
Seham Abou Shousha1, Suzan Baheeg2, Hossam Ghoneim1
1Medical Research Institute, Immunology and Allergy Department, Alexandria University, Alexandria, Egypt.
Breast disease
|June 19, 2023
概括
这项研究引入了一种针对瘤微环境 (TME) 的新型免疫疗法,以对抗乳腺癌. 通过阻断FasL和保护免疫细胞,这种方法显著增强了瘤细胞的亡,并减少了癌症干细胞 (CSCs).
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 癌症研究 癌症研究
背景情况:
- 瘤细胞通过瘤微环境 (TME) 逃避免疫检测.
- 瘤细胞表达的Fas连接体 (FasL) 可以诱导免疫细胞的亡,阻碍抗癌反应.
- Fas/FasL信号与维持癌症干细胞 (CSCs) 有关,促进瘤的攻击性和抵抗力.
研究的目的:
- 研究一种针对乳腺癌中FasL介导的免疫逃避的新型免疫治疗策略.
- 在TME模型中评估阻断FasL在瘤细胞和保护外周血液单核细胞 (PBMCs) 的疗效.
主要方法:
- 利用模仿TME的组织培养系统.
- 采用重组Fas (rFas) 分子来阻断瘤细胞上过度表达的FasL.
- 补充了PBMCs的培养物,先用抗Fas单克隆抗体 (mAb) 进行预处理,以保护它们免受瘤反击.
主要成果:
- 在用rFas分子和抗Fas PBMCs治疗的培养物中观察到显著增加的瘤细胞亡.
- 记录了CD44表达的显著下降,这是CSC的标志物.
- 与对照组相比,经过rFas丰富和抗Fas治疗的PBMC丰富培养都显示出增强的抗瘤作用.
结论:
- 拟议的免疫治疗策略显示,通过克服免疫逃避来治疗乳腺癌具有前途.
- 阻断FasL和保护免疫细胞可以增强抗瘤免疫力并抑制癌症干细胞.
- 这种方法需要进一步研究,作为乳腺癌的潜在治疗方法.
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