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Cancer Immunology, Immunotherapy

, Volume 59, Issue 10, pp 1573–1582 | Cite as

Toll-like receptor expression and function in human dendritic cell subsets: implications for dendritic cell-based anti-cancer immunotherapy

  • Gerty Schreibelt
  • Jurjen Tel
  • Kwinten H. E. W. J. Sliepen
  • Daniel Benitez-Ribas
  • Carl G. Figdor
  • Gosse J. Adema
  • I. Jolanda M. de VriesEmail author
Focussed Research Review

Abstract

Dendritic cells (DCs) are central players of the immune response. To date, DC-based immunotherapy is explored worldwide in clinical vaccination trials with cancer patients, predominantly with ex vivo-cultured monocyte-derived DCs (moDCs). However, the extensive culture period and compounds required to differentiate them into DCs may negatively affect their immunological potential. Therefore, it is attractive to consider alternative DC sources, such as blood DCs. Two major types of naturally occurring DCs circulate in peripheral blood, myeloid DCs (mDCs) and plasmacytoid (pDCs). These DC subsets express different surface molecules and are suggested to have distinct functions. Besides scavenging pathogens and presenting antigens, DCs secrete cytokines, all of which is vital for both the acquired and the innate immune system. These immunological functions relate to Toll-like receptors (TLRs) expressed by DCs. TLRs recognize pathogen-derived products and subsequently provoke DC maturation, antigen presentation and cytokine secretion. However, not every TLR is expressed on each DC subset nor causes the same effects when activated. Considering the large amount of clinical trials using DC-based immunotherapy for cancer patients and the decisive role of TLRs in DC maturation, this review summarizes TLR expression in different DC subsets in relation to their function. Emphasis will be given to the therapeutic potential of TLR-matured DC subsets for DC-based immunotherapy.

Keywords

Dendritic cell vaccination Myeloid dendritic cells Plasmacytoid dendritic cells Toll-like receptors 

Notes

Acknowledgments

This work was supported by grants from the Dutch Cancer Society (KWF 2003-2917, KWF 2004-3126, KWF 2004-3127, KWF 2006-3699), the Netherlands Organization for Scientific Research (NWO ZonMW, Vidi grant 917.76.363, Vici grant 918.66.615), the TIL-foundation, the NOTK-foundation and the EU (Cancerimmunotherapy, LSHC-CT-2006-518234 and DC-Thera, LSHB-CT-2004-512074).

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Gerty Schreibelt
    • 1
  • Jurjen Tel
    • 1
  • Kwinten H. E. W. J. Sliepen
    • 1
  • Daniel Benitez-Ribas
    • 2
  • Carl G. Figdor
    • 1
  • Gosse J. Adema
    • 1
  • I. Jolanda M. de Vries
    • 1
    • 3
    • 4
    Email author
  1. 1.Department of Tumor Immunology, Nijmegen Centre for Molecular Life SciencesRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  2. 2.Department of GastroenterologyCIBERehd, Hospital ClinicBarcelonaSpain
  3. 3.Department of Medical OncologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  4. 4.Department of Paedriatric Hemato-OncologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands

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