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Type-1 polarized dendritic cells primed for high IL-12 production show enhanced activity as cancer vaccines

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A Protocol for this article was published on 18 January 2018

Abstract

While multiple pathways of dendritic cell (DC) maturation result in transient production of IL-12, fully mature DCs show reduced ability to produce IL-12p70 upon a subsequent interaction with Ag-specific T cells, limiting their in vivo performance as vaccines. Such “DC exhaustion” can be prevented by the presence of IFNγ during the maturation of human DCs (type-1-polarization), resulting in improved induction of tumor-specific Th1 and CTL responses in vitro. Here, we show that type-1 polarization of mouse DCs strongly enhances their ability to induce CTL responses against a model tumor antigen, OVA, in vivo, promoting the induction of protective immunity against OVA-expressing EG7 lymphoma. Interestingly, in contrast to the human system, the induction of mouse DC1s requires the participation of IL-4, a nominal Th2-inducing cytokine. The current data help to explain the previously reported Th1-driving and anti-tumor activities of IL-4, and demonstrate that type-1 polarization increases in vivo activity of DC-based vaccines.

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Acknowledgments

The authors thank Dr. Pia Bjork for stimulating discussions and Erik Berk for critically reading the manuscript. This work was supported by the NIH grants CA095128 and CA101944.

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Correspondence to Pawel Kalinski.

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Adam S. Giermasz and Julie A. Urban contributed equally to this work.

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Giermasz, A.S., Urban, J.A., Nakamura, Y. et al. Type-1 polarized dendritic cells primed for high IL-12 production show enhanced activity as cancer vaccines. Cancer Immunol Immunother 58, 1329–1336 (2009). https://doi.org/10.1007/s00262-008-0648-5

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  • DOI: https://doi.org/10.1007/s00262-008-0648-5

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