Type-1 polarized dendritic cells primed for high IL-12 production show enhanced activity as cancer vaccines |
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Authors: | Adam S. Giermasz,Julie A. Urban,Yutaro Nakamura,Payal Watchmaker,Rachel L. Cumberland,William Gooding,Pawel Kalinski |
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Affiliation: | (1) Department of Surgery, Hillman Cancer Center, University of Pittsburgh, UPCI Research Pavilion, Room 1.46b, 5117 Center Avenue, Pittsburgh, PA 15213-1863, USA;(2) Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15213, USA;(3) Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15213, USA;(4) Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15213, USA;(5) University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA; |
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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. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Adam S. Giermasz and Julie A. Urban contributed equally to this work. |
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Keywords: | Dendritic cells Vaccines Lymphoma Mouse IL-12 IL-4 |
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