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

doi:10.1016/j.celrep.2015.04.009

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

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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 language	English (US)
Pages (from-to)	957-966
Number of pages	10
Journal	Cell Reports
Volume	11
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2015.04.009
State	Published - May 12 2015

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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Xia, X., Mai, J., Xu, R., Perez, J. E. T., Guevara, M. L., Shen, Q., Mu, C., Tung, H. Y., Corry, D. B., Evans, S. E., Liu, X., Ferrari, M., Zhang, Z., Li, X. C., Wang, R. F., & Shen, H. (2015). Porous Silicon Microparticle Potentiates Anti-Tumor Immunity by Enhancing Cross-Presentation and Inducing Type I Interferon Response. Cell Reports, 11(6), 957-966. https://doi.org/10.1016/j.celrep.2015.04.009

Xia, X, Mai, J, Xu, R, Perez, JET, Guevara, ML, Shen, Q, Mu, C, Tung, HY, Corry, DB, Evans, SE, Liu, X, Ferrari, M, Zhang, Z , Li, XC , Wang, RF & Shen, H 2015, 'Porous Silicon Microparticle Potentiates Anti-Tumor Immunity by Enhancing Cross-Presentation and Inducing Type I Interferon Response', Cell Reports, vol. 11, no. 6, pp. 957-966. https://doi.org/10.1016/j.celrep.2015.04.009

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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.",

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

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AU - Mai, Junhua

AU - Xu, Rong

AU - Perez, Jorge Enrique Tovar

AU - Guevara, Maria L.

AU - Shen, Qi

AU - Mu, Chaofeng

AU - Tung, Hui Ying

AU - Corry, David B.

AU - Evans, Scott E.

AU - Liu, Xuewu

AU - Ferrari, Mauro

AU - Zhang, Zhiqiang

AU - Li, Xian Chang

AU - Wang, Rong Fu

AU - Shen, Haifa

PY - 2015/5/12

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N2 - 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.

AB - 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.

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

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