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Functional evaluation of dendritic cells and extracellular vesicles as immunotherapy for breast cancer

Oncogene volume 43, pages 319–327 (2024)Cite this article

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Abstract

Dendritic cells (DCs) play critical roles in recognizing and presenting antigens to T cells. They secrete dendritic cell-derived extracellular vesicles (DC-sEVs), which could mimic the function of DCs. Therefore, we explore the possibility of using DC-sEVs as a potential personalized vaccine in this study. We compared the efficacy of DCs and DC-sEVs on stimulating the immune system to target breast cancer cells and found that DC-sEVs had significantly more MHC molecules on the surface when compared to the parental DCs. In our in vivo and in vitro testing, Dc-sEVs showed significant advantages over DCs, regarding efficacy, safety, storage, and potential delivery advantages. DC-sEVs were able to suppress the growth of immune-cold breast tumors, while DCs failed to do so. These results indicate the strong potential utility of DC-sEVs as a personalized immunotherapy for breast cancer.

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Fig. 1: MHC I and MHC II are retained and enriched on the surface of DC-sEVs.
Fig. 2: In vitro comparison of antigen-presentation abilities between DC-sEVs and DCs.
Fig. 3: Comparison of biodistribution and adverse effects between DC-sEVs and DCs in vivo.
Fig. 4: Comparison of anti-tumor effect between DC-sEVs and DCs in vivo.
Fig. 5: Comparison of anti-tumor effect between DC-sEVs and DCs in immune-cold 4T1 tumor.

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Acknowledgements

We thank Dr. Ravi Nandan Singh, Ph.D. (Wake Forest University) for kindly providing the assistance in NTA of the sEVs. This work was supported by NIH grants RO1CA173499, R01CA185650, R01CA205067, and W81XWH2110075 from the Department of Defense (to K Watabe), and NIH T32CA247819 (to K Wu). This study used various Core Facilities and Departmental Shared Equipment resources including Cellular Imaging Shared Resources, Tumor Tissue and Pathology Shared Resource Cell and Viral Vector Core Laboratory and FC Shared Resources that are supported by the Comprehensive Cancer Center of Wake Forest University NCI, National Institutes of Health Grant (P30CA012197).

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Author notes

  1. These authors contributed equally: Feng Lyu, Kerui Wu.

Authors and Affiliations

  1. Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA

    Feng Lyu, Kerui Wu, Shih-Ying Wu, Ravindra Pramod Deshpande, Abhishek Tyagi, Isabella Ruiz & Kounosuke Watabe

  2. Department of Breast Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University; People’s Hospital of Henan University, 450003, Zhengzhou, Henan, China

    Feng Lyu

  3. Department of Nanoscience, The Joint School of Nanoscience and Nanoengineering, University of North Carolina Greensboro, Greensboro, NC, 27401, USA

    Kerui Wu & Sindhu Yalavarthi

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  1. Feng Lyu
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Contributions

Conception and design: FL, K Wu, K Watabe. Development of methodology: FL, K Wu, K Watabe. Acquisition of data (provided animals, acquired and managed patient specimens, provided facilities, etc.): FL, K Wu, SYW, RS, RPD, AT, IR, SY, K Watabe. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): FL, K Wu, SYW, K Watabe. Writing, review, and/or revision of the manuscript: FL, K Wu, IR, SY, K Watabe. Administrative, technical, or material support: K Wu, RPD, K Watabe. Study supervision: K Watabe.

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Correspondence to Kounosuke Watabe.

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Lyu, F., Wu, K., Wu, SY. et al. Functional evaluation of dendritic cells and extracellular vesicles as immunotherapy for breast cancer. Oncogene 43, 319–327 (2024). https://doi.org/10.1038/s41388-023-02893-2

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