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

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.

Keywords

Dendritic cells Tumor Immunotherapy Toll-like receptor Cancer vaccine 

Abbreviations

CTL

Cytotoxic T lymphocyte

DC

Dendritic cell

FL-DC

Flt3L-derived DC

Flt3L

Fms-like tyrosine kinase 3 ligand

mDC

Myeloid DC

OVA

Ovalbumin

pDC

Plasmacytoid DC

TLR

Toll-like receptor

Treg cell

Regulatory T cell

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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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