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

  • Focussed Research Review
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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.

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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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Correspondence to I. Jolanda M. de Vries.

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This paper is a Focussed Research Review based on a presentation given at the Ninth International Conference on Progress in Vaccination against Cancer (PIVAC 9), held in Sofia, Bulgaria, 8–10 October 2009.

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Schreibelt, G., Tel, J., Sliepen, K.H.E.W.J. et al. Toll-like receptor expression and function in human dendritic cell subsets: implications for dendritic cell-based anti-cancer immunotherapy. Cancer Immunol Immunother 59, 1573–1582 (2010). https://doi.org/10.1007/s00262-010-0833-1

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