Toll-like receptor expression and function in human dendritic cell subsets: implications for dendritic cell-based anti-cancer immunotherapy |
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Authors: | Gerty Schreibelt Jurjen Tel Kwinten H E W J Sliepen Daniel Benitez-Ribas Carl G Figdor Gosse J Adema I Jolanda M de Vries |
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Institution: | (1) Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands;(2) Department of Gastroenterology, CIBERehd, Hospital Clinic, Barcelona, Spain;(3) Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands;(4) Department of Paedriatric Hemato-Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; |
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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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