研究动态
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骨和软组织肉瘤中外泌体 PD-L1 的释放及其与放射治疗的关系。

Release of Exosomal PD-L1 in Bone and Soft Tissue Sarcomas and Its Relationship to Radiotherapy.

发表日期:2024 Jul 08
作者: Keisuke Yoshida, Kunihiro Asanuma, Yumi Matsuyama, Takayuki Okamoto, Tomohito Hagi, Tomoki Nakamura, Akihiro Sudo
来源: Cancers

摘要:

(1)背景:外泌体PD-L1因其在引发全身免疫抑制中的作用而受到关注。本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性外泌体 PD-L1 的能力以及放疗 (RT) 是否诱导外泌体 PD-L1 释放。 (2)方法:采用人骨肉瘤细胞系143B和人纤维肉瘤细胞系HT1080。通过超速离心从培养基和血液中分离外泌体。评估了肿瘤细胞和外泌体上 PD-L1 的表达。利用对 PBMC 的抑制作用来评估外泌体 PD-L1 的活性。放疗后,比较 PD-L1 表达的变化。 (3)结果:肿瘤细胞培养基中检测到外泌体PD-L1,而PD-L1敲除细胞培养基中不存在外泌体PD-L1。外泌体 PD-L1 对 PBMC 活化表现出抑制作用。在荷瘤小鼠的血液中检测到人源性外泌体 PD-L1。放疗后,肿瘤细胞上调 PD-L1,并在血流中检测到人源性外泌体 PD-L1。 (4)结论:外泌体PD-L1源自骨和软组织肉瘤细胞,并播散到循环系统中。 RT 照射后,肿瘤细胞中的 PD-L1 水平和外泌体 PD-L1 的释放增加。
(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.