TY - JOUR
T1 - Outer Membrane Vesicle-Based Nanohybrids Target Tumor-Associated Macrophages to Enhance Trained Immunity-Related Vaccine-Generated Antitumor Activity
AU - Liang, Jie
AU - Zhu, Fei
AU - Cheng, Keman
AU - Ma, Nana
AU - Ma, Xiaotu
AU - Feng, Qingqing
AU - Xu, Chen
AU - Gao, Xiaoyu
AU - Wang, Xinwei
AU - Shi, Jian
AU - Zhao, Xiao
AU - Nie, Guangjun
N1 - Publisher Copyright:
© 2023 Wiley-VCH GmbH.
PY - 2023/11/16
Y1 - 2023/11/16
N2 - 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.
AB - 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.
KW - antitumor mechanisms
KW - outer membrane vesicle-based nanohybrids
KW - trained immunity signatures
KW - trained immunity-related vaccines (TIrV)
KW - tumor-associated macrophages (TAMs)
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U2 - 10.1002/adma.202306158
DO - 10.1002/adma.202306158
M3 - Article
AN - SCOPUS:85174150208
SN - 0935-9648
VL - 35
JO - Advanced Materials
JF - Advanced Materials
IS - 46
M1 - 2306158
ER -