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Cancer Immunology, Immunotherapy

, Volume 58, Issue 8, pp 1329–1336 | Cite as

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

  • Adam S. Giermasz
  • Julie A. Urban
  • Yutaro Nakamura
  • Payal Watchmaker
  • Rachel L. Cumberland
  • William Gooding
  • Pawel KalinskiEmail author
Original Article

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.

Keywords

Dendritic cells Vaccines Lymphoma Mouse IL-12 IL-4 

Notes

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.

Supplementary material

262_2008_648_MOESM1_ESM.tif (315 kb)
Supplementary material 1 (TIF 315 kb)
262_2008_648_MOESM2_ESM.tif (317 kb)
Supplementary material 1 (TIF 317 kb)

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Adam S. Giermasz
    • 1
  • Julie A. Urban
    • 1
  • Yutaro Nakamura
    • 1
  • Payal Watchmaker
    • 1
  • Rachel L. Cumberland
    • 1
  • William Gooding
    • 4
    • 5
  • Pawel Kalinski
    • 1
    • 2
    • 3
    • 5
    Email author
  1. 1.Department of SurgeryHillman Cancer Center, University of PittsburghPittsburghUSA
  2. 2.Department of ImmunologyUniversity of PittsburghPittsburghUSA
  3. 3.Department of Infectious Diseases and MicrobiologyUniversity of PittsburghPittsburghUSA
  4. 4.Department of BiostatisticsUniversity of PittsburghPittsburghUSA
  5. 5.University of Pittsburgh Cancer InstitutePittsburghUSA

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