期刊
BRITISH JOURNAL OF CANCER
卷 129, 期 6, 页码 925-934出版社
SPRINGERNATURE
DOI: 10.1038/s41416-023-02369-w
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This study found that PD-L1-positive sEVs in head and neck squamous cell carcinoma patients have different cellular origins, including tumor cells, T cells, B cells, dendritic cells, and monocyte/macrophages. However, PD-L1-positive sEVs derived from immune cells do not have immunosuppressive effects due to the co-expression of CD80. The co-expression of CD80 restricts the immunosuppressive effect of sEV PD-L1.
BackgroundThe 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.MethodssEVs 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.ResultsPD-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.ConclusionThe 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.
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