State 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, 430079, Wuhan, China.
Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, 430079, Wuhan, China.
Br J Cancer. 2023 Oct;129(6):925-934. doi: 10.1038/s41416-023-02369-w. Epub 2023 Aug 2.
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.
肿瘤细胞来源的小细胞外囊泡（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。本研究旨在测试免疫细胞是否释放具有免疫抑制作用的 PD-L1 阳性 sEVs。
从小头颈部鳞状细胞癌（HNSCC）患者的不同临床样本中分离 sEVs，评估 PD-L1 阳性 sEVs 的水平和细胞来源。检测 PD-L1 阳性 sEVs 上 CD80 的共表达，以评估其免疫抑制和肿瘤促进作用。
HNSCC 患者的 PD-L1 阳性 sEVs 具有多种细胞来源，包括肿瘤细胞、T 细胞、B 细胞、树突状细胞和单核细胞/巨噬细胞。然而，由于 CD80 的共表达，来自免疫细胞的 PD-L1 阳性 sEVs 没有发挥免疫抑制功能。研究证实 CD80 的共表达破坏了 sEV PD-L1 与 T 细胞上其受体 PD-1 的结合，并减弱了 sEV PD-L1 介导的免疫抑制作用，无论是在体外还是体内。
本研究表明 PD-L1 阳性 sEVs 具有细胞来源和功能异质性。CD80 的共表达可以限制 sEV PD-L1 的免疫抑制作用。需要进一步了解 PD-L1 阳性 sEV 亚群，以进一步提高其临床应用。
