Outer Membrane Vesicle‐Based Nanohybrids Target Tumor‐Associated Macrophages to Enhance Trained Immunity‐Related Vaccine‐Generated Antitumor Activity
Open accessAbstract
Trained immunity refers to the innate immune system building memory‐like features in response to subsequent infections and vaccinations. Compared with classical tumor vaccines, trained immunity‐related vaccines (TIrV) are independent of tumor‐specific antigens. Bacterial outer membrane vesicles (OMVs) contain an abundance of PAMPs and have the potential to act as TIrV‐inducer, but face challenges in endotoxin tolerance, systemic delivery, long‐term training, and trained tumor‐associated macrophage (TAM)‐mediated antitumor phagocytosis. Here, an OMV‐based TIrV is developed, OMV nanohybrids (OMV‐SIRPα@CaP/GM‐CSF) for exerting vaccine‐enhanced antitumor activity. In the bone marrow, GM‐CSF‐assisted OMVs train bone marrow progenitor cells and monocytes, which are inherited by TAMs. In tumor tissues, SIRPα‐Fc‐assisted OMVs trigger TAM‐mediated phagocytosis. This TIrV can be identified by metabolic and epigenetic rewiring using transposase‐accessible chromatin (ATAC) and transcriptome sequencing. Furthermore, it is found that the TIrV‐mediated antitumor mechanism in the MC38 tumor model (TAM‐hot and T cell‐cold) is trained immunity and activated T cell response, whereas in the B16‐F10 tumor model (T cell‐hot and TAM‐cold) is primarily mediated by trained immunity. This study not only develops and identifies OMV‐based TIrV, but also investigates the trained immunity signatures and therapeutic mechanisms, providing a basis for further vaccination strategies.
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Even with nanotechnology, the efficiency of targeting disease or disordered area cells with EVs is quite low.
“To treat CNS disorders using EVs, EVs should only target the disease or disordered area cells, but even with nanotechnology, efficiency is quite low [333–336].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [336]
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- Authors
- Liang, J., Zhu, F., Cheng, K., Ma, N., Ma, X., Feng, Q., Xu, C., Gao, X., Wang, X., Shi, J., Zhao, X., & Nie, G.
- Affiliations
- Chinese Academy of Sciences (CN)
- National Center for Nanoscience and Technology (CN)
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China 11 Beiyitiao, Zhongguancun Beijing 100190 China
- Corresponding author
- Zhao, Xiao
- Nie, Guangjun
- ORCID
- Venue
- Advanced Materials
- Publisher
- Wiley
- Published
- 2023-10-15
- Volume
- 35
- Issue
- 46
- Pages
- e2306158-e2306158
- ISSN
- 0935-9648 (ISSN-L)
- 1521-4095
- OpenAlex
- W4386241555
- Cited by
- 84
- References
- 52
- Citations by year
- 2026: 25 · 2025: 40 · 2024: 19
- FWCI
- 9.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Advanced Materials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key Research and Development Program of China (2022YFB3808100, 2021YFA0909900)
- Natural Science Foundation of Beijing Municipality (Z200020)
- National Natural Science Foundation of China (T2288102, 31820103004, 32171384, 32222045)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- trained immunity, outer membrane vesicles, tumor-associated macrophages, hybrid nanostructures, SIRPα, GM-CSF, bone marrow progenitor cells, antitumor immunity, cancer vaccines, T cell response, MC38 tumor, epigenetic rewiring
- MeSH terms
- Extracellular Vesicles, Tumor-Associated Macrophages, Trained Immunity, Granulocyte-Macrophage Colony-Stimulating Factor, Cancer Vaccines
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