(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.
（1）背景：外泌体PD-L1因其在引发系统性免疫抑制中的作用而备受关注。本研究旨在阐明骨与软组织肉瘤细胞是否具备分泌功能性活性外泌体PD-L1的能力，以及放射治疗（RT）是否会诱导外泌体PD-L1的释放。（2）方法：实验采用人骨肉瘤细胞系143B和人纤维肉瘤细胞系HT1080。通过超速离心法从培养基和血液中分离外泌体。评估肿瘤细胞及外泌体表面PD-L1的表达情况。采用对PBMC的抑制效应来评估外泌体PD-L1的活性。比较放射治疗后PD-L1表达的变化。（3）结果：在肿瘤细胞培养基中检测到外泌体PD-L1，而在PD-L1敲除细胞的培养基中未检出。外泌体PD-L1对PBMC活化表现出抑制作用。在荷瘤小鼠血液中检测到人源外泌体PD-L1。放射治疗后，肿瘤细胞PD-L1表达上调，且血液中可检测到人源外泌体PD-L1。（4）结论：外泌体PD-L1源自骨与软组织肉瘤细胞，并释放进入循环系统。经放射治疗后，肿瘤细胞内PD-L1水平及外泌体PD-L1的释放量均显著增加。
Release of Exosomal PD-L1 in Bone and Soft Tissue Sarcomas and Its Relationship to Radiotherapy
肿瘤(癌症)患者之家