Abstract:
: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.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
den Brok MH,Sutmuller RP,Nierkens S,Bennink EJ,Frielink C,Toonen LW,Boerman OC,Figdor CG,Ruers TJ,Adema GJdoi
10.1038/sj.bjc.6603341subject
Has Abstractpub_date
2006-10-09 00:00:00pages
896-905issue
7eissn
0007-0920issn
1532-1827pii
6603341journal_volume
95pub_type
杂志文章abstract::The hypothesis is advanced that abnormalities of the chromosome group 17,18 play a special role in the genesis and/or evolution of some reticuloendothelial neoplasms. Aberrations of the group 17,18 chromosomes in tumour cells exceed in variety the reported anomaliesof any other chromosome. Both the frequency of these ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1970.11
更新日期:1970-03-01 00:00:00
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journal_title:British journal of cancer
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更新日期:2006-04-10 00:00:00
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pub_type: 杂志文章,多中心研究,随机对照试验
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pub_type: 杂志文章
doi:10.1038/bjc.1992.403
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1986-04-01 00:00:00
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更新日期:2003-08-18 00:00:00
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journal_title:British journal of cancer
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doi:10.1038/bjc.1996.663
更新日期:1996-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:1998-02-01 00:00:00
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更新日期:2019-04-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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