骨髓瘤中PD-1互动组:确定了人类和狗之间保存的新型PD-1/AXL相互作用
Katarzyna Dziubek1, Jakub Faktor1, Kiran Bharat Lokhande2,3
1International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland.
Cell communication and signaling : CCS
|December 19, 2024
概括
编程细胞死亡蛋白1 (PD-1) 与骨髓癌细胞中的铁氨酸激酶受体AXL相互作用. 这种PD-1/AXL相互作用在狗中保留着,这表明它是新型癌症免疫疗法的潜在标.
科学领域:
- 免疫学和癌症生物学
- 分子和细胞生物学分子和细胞生物学
- 蛋白质组学和结构生物学
背景情况:
- 针对PD-1/PD-L1的免疫检查点抑制剂已经改变了癌症治疗,但骨肉瘤仍然具有挑战性.
- 除了免疫细胞之外,PD-1在癌细胞中的作用尚未完全理解,特别是其蛋白质相互作用.
- 在癌细胞中研究PD-1的互动组可能会揭示新的治疗点.
研究的目的:
- 为了研究PD-1在人类骨髓瘤细胞中的表达和蛋白质-蛋白质相互作用.
- 描述PD-1与氨酸激酶受体AXL之间的分子相互作用.
- 为了验证PD-1/AXL相互作用在犬类骨髓瘤作为一个翻译模型.
主要方法:
- 西方涂抹,流细胞计和免疫光学用于PD-1表达和定位.
- 高通量蛋白质组学 (拉向测定,质谱) 用于识别PD-1相互作用蛋白.
- 免疫阻塞,近距离结合试验 (PLA),分子动力学 (MD) 模拟和PD-1/AXL相互作用的抑制剂研究.
- 在狗骨髓瘤细胞系中分析PD-1和AXL表达和相互作用.
主要成果:
- PD-1在人体骨髓瘤细胞中表达,无论是细胞内还是细胞表面.
- 鉴定出AXL是一种新型的PD-1相互作用蛋白在骨髓瘤细胞中.
- 分子动力学模拟显示了PD-1和AXL之间强烈的结合亲缘关系,特别是涉及细胞内域.
- 在狗骨髓瘤细胞中证实了PD-1/AXL相互作用,在物种之间保留了相互作用的残留物.
- 作为AXL抑制剂的bemcentinib降低了PD-1/AXL的结合亲和力,但没有消除.
结论:
- PD-1/AXL相互作用代表了骨髓瘤中一种新的分子途径.
- 这种在人类和狗骨髓瘤之间相互作用的保存性强调了它的生物学意义.
- 了解PD-1/AXL相互作用为开发针对骨髓瘤的新免疫治疗策略提供了基础.
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