肿瘤细胞来源的小型细胞外囊泡(sEVs)上的PD-L1可以抑制T细胞的增殖和细胞因子产生。然而，PD-L1也可以由非肿瘤细胞表达。本研究旨在检验免疫细胞释放免疫抑制性PD-L1阳性sEVs。我们从头颈鳞癌(HNSCC)患者的不同临床样本中分离出sEVs，并评估了PD-L1阳性sEVs的水平和细胞起源。我们检查了PD-L1阳性sEVs上CD80的共表达，以评估其免疫抑制和肿瘤促进效果。在HNSCC患者中，PD-L1阳性sEVs具有多种细胞起源，包括肿瘤细胞、T细胞、B细胞、树突状细胞和单核/巨噬细胞。然而，免疫细胞源性的PD-L1阳性sEVs由于CD80的共表达不产生免疫抑制功能。验证了CD80的共表达破坏了sEV PD-L1与T细胞上其受体PD-1的结合，减弱了sEV PD-L1介导的免疫抑制作用，无论是体外还是体内。本研究表明，PD-L1阳性sEVs具有多种细胞起源和功能异质性。CD80的共表达可以限制sEV PD-L1的免疫抑制效应。为了进一步改进它们的临床应用，需要更好地理解PD-L1阳性sEV亚群。© 2023. 作者，独家许可给斯普林格自然出版集团有限公司。

The PD-L1 on tumor cell-derived small extracellular vesicles (sEVs) can suppress the proliferation and cytokine production of T cells. However, PD-L1 can also be expressed by non-tumor cells. The present study is designed to test whether immunocytes release immunosuppressive PD-L1-positive sEVs.sEVs were isolated from different clinical samples of head and neck squamous cell carcinoma (HNSCC) patients, the level and cellular origins of PD-L1-positive sEVs were assessed. Co-expression of CD80 on PD-L1-positive sEVs was examined to evaluate the immunosuppressive and tumor-promotive effects.PD-L1-positive sEVs in HNSCC patients had various cellular origins, including tumor cell, T cell, B cell, dendritic cell and monocyte/macrophage. However, PD-L1-positive sEVs derived from immune cells did not exert immunosuppressive functions due to the co-expression of CD80. It was verified that co-expression of CD80 disrupted the binding of sEV PD-L1 to its receptor PD-1 on T cells and attenuated the immunosuppression mediated by sEV PD-L1 both in vitro and in vivo.The study suggests that PD-L1-positive sEVs have the cellular origin and functional heterogeneity. Co-expression of CD80 could restrict the immunosuppressive effect of sEV PD-L1. A greater understanding of PD-L1-positive sEV subsets is required to further improve their clinical application.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.