Cancer Immunology, Immunotherapy

, Volume 58, Issue 6, pp 901–913 | Cite as

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

  • Cornelia Wurzenberger
  • Viktor H. Koelzer
  • Susanne Schreiber
  • David Anz
  • Angelika M. Vollmar
  • Max Schnurr
  • Stefan Endres
  • Carole Bourquin
Original Article


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.


Dendritic cells Tumor Immunotherapy Toll-like receptor Cancer vaccine 



Cytotoxic T lymphocyte


Dendritic cell


Flt3L-derived DC


Fms-like tyrosine kinase 3 ligand


Myeloid DC




Plasmacytoid DC


Toll-like receptor

Treg cell

Regulatory T cell



This study was supported by grants from the Else-Kröner Fresenius Foundation (Carole Bourquin and Stefan Endres), the Deutsche Krebshilfe (10-2214-En3 to Stefan Endres, Max-Eder research fellowship to Max Schnurr), the German Research Foundation (DFG En 169/7-2 to Stefan Endres and Carole Bourquin, Graduiertenkolleg 1202 to Carole Bourquin, Stefan Endres, and Max Schnurr, SFB-TR 36 to Stefan Endres) and from LMUexcellent (cluster CiPSM 114 and research professorship to Stefan Endres). We thank Nadja Sandholzer for her expert technical assistance and Jiwu Wei and Raffaela Tyroller for providing survivin protein.


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Cornelia Wurzenberger
    • 1
  • Viktor H. Koelzer
    • 1
  • Susanne Schreiber
    • 1
  • David Anz
    • 1
  • Angelika M. Vollmar
    • 2
  • Max Schnurr
    • 3
  • Stefan Endres
    • 1
  • Carole Bourquin
    • 1
  1. 1.Division of Clinical Pharmacology, Department of Internal MedicineLudwig-Maximilian University of MunichMunichGermany
  2. 2.Department of Pharmacy, Center for Drug ResearchLudwig-Maximilian University of MunichMunichGermany
  3. 3.Department of Internal MedicineLudwig-Maximilian University of MunichMunichGermany

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