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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 6/2009

01-06-2009 | Original Article

Short-term activation induces multifunctional dendritic cells that generate potent antitumor T-cell responses in vivo

Authors: Cornelia Wurzenberger, Viktor H. Koelzer, Susanne Schreiber, David Anz, Angelika M. Vollmar, Max Schnurr, Stefan Endres, Carole Bourquin

Published in: Cancer Immunology, Immunotherapy | Issue 6/2009

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Abstract

Dendritic cell (DC) vaccines have emerged as a promising strategy to induce antitumoral cytotoxic T cells for the immunotherapy of cancer. The maturation state of DC is of critical importance for the success of vaccination, but the most effective mode of maturation is still a matter of debate. Whereas immature DC carry the risk of inducing tolerance, extensive stimulation of DC may lead to DC unresponsiveness and exhaustion. In this study, we investigated how short-term versus long-term DC activation with a Toll-like receptor 9 agonist influences DC phenotype and function. Murine DC were generated in the presence of the hematopoietic factor Flt3L (FL-DC) to obtain both myeloid and plasmacytoid DC subsets. Short activation of FL-DC for as little as 4 h induced fully functional DC that rapidly secreted IL-12p70 and IFN-α, expressed high levels of costimulatory and MHC molecules and efficiently presented antigen to CD4 and CD8 T cells. Furthermore, short-term activated FL-DC overcame immune suppression by regulatory T cells and acquired high migratory potential toward the chemokine CCL21 necessary for DC recruitment to lymph nodes. In addition, vaccination with short-term activated DC induced a strong cytotoxic T-cell response in vivo and led to the eradication of tumors. Thus, short-term activation of DC generates fully functional DC for tumor immunotherapy. These results may guide the design of new protocols for DC generation in order to develop more efficient DC-based tumor vaccines.
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Metadata
Title
Short-term activation induces multifunctional dendritic cells that generate potent antitumor T-cell responses in vivo
Authors
Cornelia Wurzenberger
Viktor H. Koelzer
Susanne Schreiber
David Anz
Angelika M. Vollmar
Max Schnurr
Stefan Endres
Carole Bourquin
Publication date
01-06-2009
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 6/2009
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-008-0606-2

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