Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity
| Autor: | Otto C. Boerman, Erik Bennink, M H M G M den Brok, Roger P.M. Sutmuller, Gosse J. Adema, Liza W.J. Toonen, Theo J.M. Ruers, Cathelijne Frielink, Stefan Nierkens, Carl G. Figdor |
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| Rok vydání: | 2006 |
| Předmět: |
regulatory T cell
Cancer Research dendritic cell Regulatory T cell medicine.medical_treatment Aetiology screening and detection [ONCOL 5] Biology Cancer Vaccines Cryosurgery Lymphocyte Depletion Mice Antigen Antigens Neoplasm Immune Regulation [NCMLS 2] Translational research [ONCOL 3] In vivo medicine Animals Antigen-presenting cell Lymph node Cell Differentiation Immunotherapy gene therapy and transplantation [UMCN 1.4] Dendritic Cells Neoplasms Experimental Immunotherapy Dendritic cell vaccination Flow Cytometry cryo ablation Mice Inbred C57BL Pathogenesis and modulation of inflammation [N4i 1] medicine.anatomical_structure Oncology CTLA-4 Immunology Catheter Ablation Cancer research Female radiofrequency ablation Lymph Nodes Microbial pathogenesis and host defense [UMCN 4.1] Translational Therapeutics Immunity infection and tissue repair [NCMLS 1] |
| Zdroj: | British Journal of Cancer, 95, 896-905 British Journal of Cancer, 95, 7, pp. 896-905 British Journal of Cancer |
| ISSN: | 0007-0920 |
| Popis: | Contains fulltext : 49400.pdf (Publisher’s version ) (Closed access) 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 with model antigens demonstrate that upon tumour destruction by radiofrequency ablation, up to 7% of the total draining lymph node (LN) DC contained antigen, whereas only few DC from the conventional vaccine reached the LN. Interestingly, following cryo ablation the amount of antigen-loaded DC is almost doubled. Analysis of surface markers revealed that both destruction methods were able to induce DC maturation. Finally, we show that in situ tumour ablation can be efficiently combined with immune modulation by anti-CTLA-4 antibodies or regulatory T-cell depletion. These combination treatments protected mice from the outgrowth of tumour challenges, and led to in vivo enhancement of tumour-specific T-cell numbers, which produced more IFN-gamma upon activation. Therefore, in situ tumour destruction in combination with immune modulation creates a unique, 'in situ DC-vaccine' that is readily applicable in the clinic without prior knowledge of tumour antigens. |
| Databáze: | OpenAIRE |
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