脂肪酸运输蛋白2对癌症中性粒细胞进行重新编程
Filippo Veglia1, Vladimir A Tyurin2, Maria Blasi3
1Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, USA.
Nature
|April 19, 2019
概括
脂肪酸运输蛋白2 (FATP2) 在多态核髓原抑制细胞 (PMN-MDSC) 中驱动免疫抑制功能. 抑制FATP2可以选择性地向这些细胞,从而提高癌症治疗的疗效,并延缓瘤的进展.
科学领域:
- 免疫学
- 癌症生物学
- 细胞代谢
背景情况:
- 多态核髓原抑制细胞 (PMN-MDSCs) 是参与癌症免疫逃避和治疗耐药性的中性粒细胞.
- 导致PMN-MDSC病态激活的确切机制尚不完全理解,这阻碍了针对性的治疗策略.
研究的目的:
- 阐明PMN-MDSC免疫抑制功能的分子机制.
- 确定和验证PMN-MDSC的选择性治疗标.
主要方法:
- 在小鼠和人类PMN-MDSC中基因表达的比较分析.
- 通过基因删除和药物抑制研究了脂肪酸运输蛋白2 (FATP2) 在PMN-MDSC功能中的作用.
- 在临床前模型中评估FATP2调节对瘤进展的影响,包括与检查点抑制剂的联合治疗.
主要成果:
- 通过GM-CSF和STAT5信号控制的PMN-MDSC仅对FATP2进行上调.
- 删除FATP2消除了PMN-MDSC抑制活性,主要通过调节酸摄取和前列腺素E2合成.
- 在与检查点抑制剂结合使用时,药理性FATP2抑制取消了PMN- MDSC功能并显著延迟了瘤生长.
结论:
- FATP2对于PMN-MDSC的免疫抑制表型至关重要.
- 选择性FATP2抑制是解除PMN-MDSC并增强癌症免疫治疗结果的有希望的策略.
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