包装在细胞外囊泡中的PD-L1阻碍了以前存在的恶性瘤中的巨介导的抗菌免疫
He-Jing Zhang1, Lingxin Zhu2, Qi-Hui Xie2
1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
瘤细胞释放携带PD-L1的囊泡,从而削弱巨细胞的抗菌免疫力. 针对这种机制可能会降低癌症患者的感染风险.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
背景情况:
- 恶性瘤通过不太了解的机制损害了系统性先天免疫力.
- 来自瘤的小细胞外囊泡 (sEVs) 与癌症进展和免疫调节有关.
研究的目的:
- 研究瘤衍生的sEVs (TEVs) 在抑制抗菌免疫中的作用.
- 阐明TEVs影响巨细胞功能和细菌清除的机制.
主要方法:
- 使用野生类型和Rab27a敲击瘤的小鼠模型来评估细菌感染耐药性.
- 向小鼠服用TEVs以评估对巨细胞介导的细菌清除和败血症的影响.
- 研究了巨细胞中受TEV包装PD-L1影响的分子信号通路 (BTK/PLCγ2).
- 在癌症患者中分析了循环sEV PD-L1水平,以确定与感染易感性的相关性.
主要成果:
- 拉布27a敲击瘤增加了对细菌感染的抵抗力.
- TEV注射损害了巨细胞的细菌清除,增加了传播,并以PD-L1依赖的方式恶化了败血症.
- 用TEV包装的PD-L1通过BTK/PLCγ2通路抑制了巨细胞化和杀死细菌.
- 循环中的sEV PD-L1水平升高预测了癌症患者的感染易感性.
- 用αPD-1治疗的患者经历的术后感染较少.
结论:
- 来自瘤的sEVs将PD-L1传递给巨细胞,抑制先天的抗菌免疫力.
- 包装在TEV中的PD-L1破坏了巨细胞化和杀死机制.
- 循环sEVPD-L1是癌症患者感染风险的潜在生物标志物.
- 针对TEV包装的PD-L1可能会减轻癌症患者的细菌感染.
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