Porous Silicon Microparticle Potentiates Anti-Tumor Immunity by Enhancing Cross-Presentation and Inducing Type I Interferon Response

Xiaojun Xia, Junhua Mai, Rong Xu, Jorge Enrique Tovar Perez, Maria L. Guevara, Qi Shen, Chaofeng Mu, Hui Ying Tung, David B. Corry, Scott E. Evans, Xuewu Liu, Mauro Ferrari, Zhiqiang Zhang, Xian Chang Li, Rong Fu Wang, Haifa Shen

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

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 localizationand 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 Tcell-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 Tcell responses. These findings highlight the potential of PSM as an immune adjuvant to potentiate DC-based cancer immunotherapy.

Original languageEnglish (US)
Pages (from-to)957-966
Number of pages10
JournalCell Reports
Volume11
Issue number6
DOIs
StatePublished - May 12 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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