PDF(Pubmed)
Abstract：
(1) Background: Exosomal PD-L1 has garnered attention owing to its role in instigating systemic immune suppression. The objective of this study is to elucidate whether bone and soft tissue sarcoma cells possess the capacity to secrete functionally active exosomal PD-L1 and whether radiotherapy (RT) induces the exosomal PD-L1 release. (2) Methods: Human osteosarcoma cell line 143B and human fibrosarcoma cell line HT1080 were utilized. Exosomes were isolated from the culture medium and blood via ultracentrifugation. The expression of PD-L1 on both tumor cells and exosomes was evaluated. The inhibitory effect on PBMC was employed to assess the activity of exosomal PD-L1. Post radiotherapy, changes in PD-L1 expression were compared. (3) Results: Exosomal PD-L1 was detected in the culture medium of tumor cells but was absent in the culture medium of PD-L1 knockout cells. Exosomal PD-L1 exhibited an inhibitory effect on PBMC activation. In tumor-bearing mice, human-derived exosomal PD-L1 was detected in the bloodstream. Following radiotherapy, tumor cells upregulated PD-L1, and human-derived exosomal PD-L1 were detected in the bloodstream. (4) Conclusions: Exosomal PD-L1 emanates from bone and soft tissue sarcoma cells and is disseminated into the circulatory system. The levels of PD-L1 in tumor cells and the release of exosomal PD-L1 were augmented after irradiation with RT.
摘要：
（1）研究背景：外泌体PD-L1因其在激发全身免疫抑制中的作用而受到关注。这项研究的目的是阐明骨和软组织肉瘤细胞是否具有分泌功能活跃的外泌体PD-L1的能力，以及放射疗法（RT）是否诱导外泌体PD-L1释放。(2)方法:利用人骨肉瘤细胞系143B和人纤维肉瘤细胞系HT1080。通过超速离心从培养基和血液中分离外泌体。评估PD-L1在肿瘤细胞和外泌体上的表达。对PBMC的抑制作用用于评估外泌体PD-L1的活性。放疗后，比较PD-L1表达的变化。（3）结果：在肿瘤细胞的培养基中检测到外泌体PD-L1，但在PD-L1敲除细胞的培养基中不存在。外泌体PD-L1表现出对PBMC活化的抑制作用。在荷瘤小鼠中，在血流中检测到人源外泌体PD-L1.放疗后，肿瘤细胞上调PD-L1,在血流中检测到人源性外泌体PD-L1.（4）结论：外泌体PD-L1从骨骼和软组织肉瘤细胞中散发，并扩散到循环系统中。RT照射后，肿瘤细胞中PD-L1的水平和外泌体PD-L1的释放增加。
