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Cellular and Molecular Biology

Immunosuppressive effect of small extracellular vesicle PD-L1 is restricted by co-expression of CD80

British Journal of Cancer volume 129, pages 925–934 (2023)Cite this article

Subjects

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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Fig. 1: Presence of PD-L1-positive sEVs in both HD and HNSCC patients.
Fig. 2: PD-L1-positive sEVs secreted by immunocytes in patients and in vitro.
Fig. 3: Different clinical significance between tumor cell- and immunocyte-derived PD-L1-positive sEVs.
Fig. 4: PD-L1-positive I-sEVs did not suppress T cells in vitro.
Fig. 5: Co-expression of CD80 on sEVs disrupted PD-L1-positive sEV-mediated PD-1 binding and T cell inhibition.
Fig. 6: Co-expression of CD80 suppressed PD-L1-positive sEV-induced immunosuppression and tumor progression in melanoma model.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the National Key R&D Program of China (2019YFA0210500), National Natural Science Foundation of China (82341023, 81922038, 81801842), Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University (TFJC2018005), The Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZLCX20212300), The Fundamental Research Funds for the Central Universities (2042022dx0003).

Author information

Author notes

  1. These authors contributed equally: Jin-Yuan Liu, Zi-Li Yu.

Authors and Affiliations

  1. 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

    Jin-Yuan Liu, Zi-Li Yu, Qiu-Yun Fu, Lin-Zhou Zhang, Jin-Bang Li, Min Wu, Bing Liu & Gang Chen

  2. Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, 430079, Wuhan, China

    Zi-Li Yu, Bing Liu & Gang Chen

  3. TaiKang Center for Life and Medical Sciences, Wuhan University, 430071, Wuhan, China

    Gang Chen

  4. Frontier Science Center for Immunology and Metabolism, Wuhan University, 430071, Wuhan, China

    Gang Chen

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Contributions

GC conceived and designed the study. JYL, ZLZ, QYF and JBL performed the experiments. JYL, ZLY, MW and BL analyzed and interpreted the data. GC, JYL and ZLY wrote and edited the manuscript. All authors approved the final version of this manuscript.

Corresponding author

Correspondence to Gang Chen.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of School and Hospital of Stomatology, Wuhan University (IRB no.2022.B05) and Zhongnan Hospital of Wuhan University (IRB no. 2021059 K). Participants gave informed consent to participate in the study before taking part. The permission for animals was approved by the Institutional Research Ethics Committee of School and Hospital of Stomatology, Wuhan University (IRB no. S07921060C).

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Liu, JY., Yu, ZL., Fu, QY. et al. Immunosuppressive effect of small extracellular vesicle PD-L1 is restricted by co-expression of CD80. Br J Cancer 129, 925–934 (2023). https://doi.org/10.1038/s41416-023-02369-w

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