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 language | English (US) |
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Pages (from-to) | 1329-1336 |
Number of pages | 8 |
Journal | Cancer Immunology, Immunotherapy |
Volume | 58 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2009 |
Externally published | Yes |
Keywords
- Dendritic cells
- IL-12
- IL-4
- Lymphoma
- Mouse
- Vaccines
ASJC Scopus subject areas
- Cancer Research
- Immunology
- Immunology and Allergy
- Oncology