免疫应对癌症的免疫反应是由树皮细胞纤维肌菌素调节的
Alexander Lubosch1, Lauren Pitt1, Caren Zoeller1
1Institute of Immunology, Heidelberg University, 69120 Heidelberg, Germany.
概括
骨髓 stromal 细胞可以抑制早期的癌症生长. 纤维素和特定的细胞标记物是这种抗癌效应的关键,这涉及髓状细胞活性.
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:
- 与癌症相关的纤维细胞 (CAFs) 了解甚少,其中一些起源于骨髓.
- 骨髓 stromal 细胞 (BMSCs) 为研究纤维细胞对癌症生长的贡献提供了多样化的来源.
研究的目的:
- 为了研究特定的骨髓 stromal 细胞种群如何调节癌症生长.
- 为了确定纤维细胞介导癌症抑制的基础机制.
主要方法:
- 使用了两种小鼠癌症模型.
- 操纵的纤维内素水平和特征化的树皮细胞群 (CD31/PECAM1,CD105/ENDOGLIN,奥斯特里克斯/SP7).
- 分析了下游的信号通路,包括整合素α5β1,TLR4和化学激素的产生.
主要成果:
- 将特定的骨髓纤维细胞添加到瘤细胞中,在小鼠模型中导致较小的病变.
- 纤维素前治疗增强了抑制;在Osterix/SP7+细胞中纤维素的遗传删除恢复了瘤生长.
- 一个抑制性树突群体缺乏CD31/PECAM1和CD105/ENDOGLIN;减少CD105/ENDOGLIN与黑色素瘤患者的生存率改善相关.
- 纤维素/片段激活了整合素α5β1和TLR4,增加了化学激素的产生,并招募了Ly6G+髓状细胞.
结论:
- 具有有益的 stromal 细胞-纤维细胞群的特征,可以抑制早期癌症生长.
- 鉴定了纤维内素驱动的髓状细胞激活作为一种关键的抗癌机制.
- 证明了针对癌症免疫疗法向肌细胞相互作用的潜力.
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