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PD-L1+ exosomes from bone marrow-derived cells of tumor-bearing mice inhibit antitumor immunity

Cellular & Molecular Immunology volume 18, pages 2402–2409 (2021)Cite this article

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Abstract

Tumors escape immune attack by upregulating the surface expression of PD-L1, which interacts with PD-1 on T cells to activate immune inhibitory signaling. Anti-PD-1 treatments can effectively block this inhibitory signaling and activate antitumor immune responses. However, anti-PD-1 treatment also has a tumor suppressive effect in patients whose tumor cells do not express PD-L1. The underlying mechanisms are poorly defined. Here, we report that exosomes from bone marrow-derived cells (BMDCs) in tumor-bearing mice, but not in healthy mice, carry PD-L1. PD-L1 on these exosomes is biofunctional and can inhibit CD8+ T cell proliferation and activation in vitro and in vivo. The transfer of exogenous exosomes from BMDCs and the inhibition of the production of endogenous exosomes by BMDCs promote and suppress tumor growth, respectively. PD-L1+ exosomes from BMDCs can be found in tumor tissues. In addition, exosomes from BMDCs promote tumor metastasis in a PD-L1-dependent manner. Therefore, our results indicate that exosomes from BMDCs play important roles in tumor immunosuppression via PD-L1.

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Fig. 1: BMDC-EXOsTu inhibit CD8+ T cell proliferation via PD-L1.
Fig. 2: BMDC-EXOsTu inhibit antitumor immunity in vivo.
Fig. 3: Inhibition of endogenous exosome release from the BMDCs improves antitumor immunity.
Fig. 4: PD-L1+ BMDC-EXOsTu can migrate into tumor tissues.
Fig. 5: BMDC-EXOsTu promote tumor metastasis.

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Acknowledgements

This work was supported by the Basic Public Welfare Projects of Zhejiang Province (LQ18C080001), the Natural Science Foundation of Zhejiang Province (LY19H100003 and LQ20H160018), and the Hangzhou Health Science and Technology Plan (OO20191170).

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  1. These authors contributed equally: Yan Sun, Jufeng Guo, Lei Yu

Authors and Affiliations

  1. Department of Infectious Disease, Childrenʼs Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Childrenʼs Regional Medical Center, 310052, Hangzhou, China

    Yan Sun & Yinghu Chen

  2. Department of Comprehensive Medical Oncology, Zhejiang Cancer Hospital, 310022, Hangzhou, China

    Yan Sun

  3. Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310020, Hangzhou, China

    Yan Sun & Xian Wang

  4. Department of Breast Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, 310006, Hangzhou, China

    Jufeng Guo

  5. Laboratory of Cancer Biology, The Key Lab of Biotherapy in Zhejiang Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310020, Hangzhou, China

    Lei Yu

  6. Department of Respiratory Medicine, Nanjing Medical University, 211166, Nanjing, China

    Tianxin Guo & Jiaoli Wang

  7. Department of Respiratory Medicine, Affiliated Hangzhou First Peopleʼs Hospital, Zhejiang University School of Medicine, 310006, Hangzhou, China

    Jiaoli Wang

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Correspondence to Xian Wang or Yinghu Chen.

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Sun, Y., Guo, J., Yu, L. et al. PD-L1+ exosomes from bone marrow-derived cells of tumor-bearing mice inhibit antitumor immunity. Cell Mol Immunol 18, 2402–2409 (2021). https://doi.org/10.1038/s41423-020-0487-7

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