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British Journal of Cancer (2006) 95, 896 905 & 2006 Cancer Research UK All rights reserved 0007 0920/06 $30.00
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Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity
Translational
Therapeutics
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Dendritic cells (DC) are crucial antigen-presenting cells (APC) for the initiation of primary T-cell responses (Adams et al, 2005; Banchereau and Palucka, 2005). Immature DC are well equipped to take up and process antigen from their surroundings, but they lack sufficient co-stimulatory signals required for productive T-cell activation. In a stimulatory environment, like in an infection, immature DC undergo activation, maturation and acquire the capacity to cross-present exogenous antigens in MHC class I. Particularly, the Toll-like receptor (TLR) family of proteins initiates the DC maturation process upon recognition of conserved pathogen-associated molecular patterns (PAMPs), like LPS or unmethylated CpG oligodeoxynucleotides. Upon maturation, costimulatory molecule and MHC-peptide complex expression increases and cytokines like IL-12 skew the functional outcome of
MHMGM den Brok*,1,2, RPM Sutmuller1, S Nierkens1, EJ Bennink1, C Frielink3, LWJ Toonen1, OC Boerman3, CG Figdor1, TJM Ruers2 and GJ Adema*,11Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen 6500 HB, The Netherlands; 2Department of Surgery, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen 6500 HB, The Netherlands; 3Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen 6500 HB, The Netherlands
Dendritic cells (DC) are professional antigen-presenting cells that play a pivotal role in the induction of immunity. Ex vivo-generated, tumour antigen-loaded mature DC are currently exploited as cancer vaccines in clinical studies. However, antigen loading and maturation of DC directly in vivo would greatly facilitate the application of DC-based vaccines. We formerly showed in murine models that radiofrequency-mediated tumour destruction can provide an antigen source for the in vivo induction of anti-tumour immunity, and we explored the role of DC herein. In this paper we evaluate radiofrequency and cryo ablation for their ability to provide an antigen source for DC and compare this with an ex vivo-loaded DC vaccine. The data obtained...