期刊
CELL REPORTS
卷 11, 期 6, 页码 957-966出版社
CELL PRESS
DOI: 10.1016/j.celrep.2015.04.009
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资金
- Department of Defense [W81XWH-09-1-0212, W81XWH-12-1-0414]
- NIH [U54CA143837, U54CA151668]
- CPRIT grant from the state of Texas [RP121071]
- Ernest Cockrell Jr. Distinguished Endowed Chair
Micro- and nanometer-size particles have become popular candidates for cancer vaccine adjuvants. However, the mechanism by which such particles enhance immune responses remains unclear. Here, we report a porous silicon microparticle (PSM)-based cancer vaccine that greatly enhances cross-presentation and activates type I interferon (IFN-I) response in dendritic cells (DCs). PSM-loaded antigen exhibited prolonged early endosome localization and enhanced cross-presentation through both proteasome-and lysosome-dependent pathways. Phagocytosis of PSM by DCs induced IFN-I responses through a TRIF-and MAVS-dependent pathway. DCs primed with PSM-loaded HER2 antigen produced robust CD8 T cell-dependent anti-tumor immunity in mice bearing HER2+ mammary gland tumors. Importantly, this vaccination activated the tumor immune microenvironment with elevated levels of intra-tumor IFN-I and MHCII expression, abundant CD11c+ DC infiltration, and tumor-specific cytotoxic T cell responses. These findings highlight the potential of PSM as an immune adjuvant to potentiate DC-based cancer immunotherapy.
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