Porous silicon microparticle potentiates anti-tumor immunity by enhancing cross-presentation and inducing type I interferon response.
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.
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
Xiaojun
X
Xia
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
Junhua
J
Mai
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
Rong
R
Xu
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
Jorge Enrique Tovar
JET
Perez
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
Maria L
ML
Guevara
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
Qi
Q
Shen
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
Chaofeng
C
Mu
Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Hui-Ying
HY
Tung
Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
David B
DB
Corry
Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Scott E
SE
Evans
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
Xuewu
X
Liu
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
Mauro
M
Ferrari
Immunobiology and Transplantation Research, Houston Methodist Research Institute, Houston, TX 77030, USA.
Zhiqiang
Z
Zhang
Immunobiology and Transplantation Research, Houston Methodist Research Institute, Houston, TX 77030, USA.
Xian Chang
XC
Li
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
Rong-Fu
RF
Wang
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: hshen@houstonmethodist.org.
Haifa
H
Shen
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007113:Immunity, Innate; D007370:Interferon Type I / Q000276:immunology*; D015674:Mammary Neoplasms, Animal / Q000473:pathology; D008810:Mice, Inbred C57BL; D008863:Microspheres; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D010587:Phagocytosis; D016062:Porosity; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D012825:Silicon / Q000737:chemistry*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D059016:Tumor Microenvironment
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007370:Interferon Type I; D010047:Ovalbumin; D018719:Erb-b2 Receptor Tyrosine Kinases; D012825:Silicon; C512612:MAVS protein, mouse; C476286:Ticam1 protein, mouse