First Author | Xia X | Year | 2015 |
Journal | Cell Rep | Volume | 11 |
Issue | 6 | Pages | 957-966 |
PubMed ID | 25937283 | Mgi Jnum | J:277591 |
Mgi Id | MGI:6274099 | Doi | 10.1016/j.celrep.2015.04.009 |
Citation | Xia X, et al. (2015) Porous silicon microparticle potentiates anti-tumor immunity by enhancing cross-presentation and inducing type I interferon response. Cell Rep 11(6):957-966 |
abstractText | 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. |