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 Kalinski

Research output: Contribution to journalArticle

64 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1329-1336
Number of pages8
JournalCancer Immunology, Immunotherapy
Volume58
Issue number8
DOIs
StatePublished - Aug 2009
Externally publishedYes

Keywords

  • Dendritic cells
  • IL-12
  • IL-4
  • Lymphoma
  • Mouse
  • Vaccines

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Immunology and Allergy
  • Oncology

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