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- W4297387612 abstract "Abstract Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies, have been successfully used to modulate the cancer killing function of immune cells in the tumor microenvironment (TME). However, in bladder cancer, the level of the proinflammatory M1 macrophages were significantly low than the immunosuppressive M2 macrophages. The abundant of M2 macrophages released cytokines to induce the resistance of ICIs treatment and alleviate immune cell attack, finally resulting in promoting tumor growth. To enhance the bladder cancer immunotherapy, nanovesicles derived from M1 macrophages (M1 NV) was applied to load the TLR7/8 agonist of R848, a potent driver of M1 macrophages, for constructing M1 NV-R848. The results revealed M1 NV-R848 could more effectively induce polarization of M2 macrophages into M1 macrophages when compared to M1 NV or R848 alone both in vitro and in vivo . In addition, intravenous injection of M1 NV-R848 would improve the immunosuppressive TME by upregulation of proinflammatory M1 macrophages, improvement of CD8+T cells infiltration, finally enhancing the immunotherapy of PD-L1 antibodies with good biocompatibility in bladder cancer bearing mouse model. Thus, our study demonstrates that M1 NV-R848 could serve as a potential strategy to improve the polarization of M1 macrophages in bladder cancer, which might be further used for other cancer with the immunosuppressive TME." @default.
- W4297387612 created "2022-09-28" @default.
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- W4297387612 date "2022-09-27" @default.
- W4297387612 modified "2023-09-27" @default.
- W4297387612 title "TLR7/8-agonist loaded M1 Macrophagederived nanovesicles promote the polarization of macrophages to enhance bladder cancer immunotherapy" @default.
- W4297387612 doi "https://doi.org/10.21203/rs.3.rs-934184/v2" @default.
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