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10.4161/21624011.2014.946360 http://scihub22266oqcxt.onion/10.4161/21624011.2014.946360 C4292219!4292219!25610730     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25610730&cmd=llinks): Failed to open stream: HTTP request failed! 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In situ loading of skin dendritic cells with apoptotic bleb-derived antigens for the induction of tumor-directed immunity |pdf=|usr=}}{{25610730}} gab.com Text In situ loading of skin dendritic cells with apoptotic bleb-derived antigens for the induction of tumor-directed immunity JO: Oncoimmunology http://www.kidney.de/pget.php?&tw=1&pmid=25610730 #FOAvip The generation and loading of dendritic cells (DC) ex-vivo for tumor vaccination purposes is laborious and costly. Direct intradermal (i.d.) administration of tumor-associated antigens could be an attractive alternative approach, provided that efficient uptake and cross-presentation by appropriately activated skin DCs can be achieved. Here, we compare the efficiency of i.d. delivery of relatively small apoptotic blebs (diameter ?0.1?1 ?m) derived from MART-1 transduced acute myeloid leukemia (AML) HL60 cells, to that of larger apoptotic cell remnants (ACR; 2?10 ?m) in a physiologically highly relevant human skin explant model. Injection of either fluorescently-labelled ACRs or blebs alone did not affect the number or distribution of migrated DC subsets from skin biopsies after 48 hours, but resulted in a general up-regulation of the co-stimulatory molecules CD83 and CD86 on skin DCs that had ingested apoptotic material. We have previously shown that i.d. administration of GM-CSF and IL-4 resulted in preferential migration of a mature and highly T cell-stimulatory CD11hiCD1a+CD14? dermal DC subset. Here, we found that co-injection of GM-CSF and IL-4 together with either ACRs or blebs resulted in uptake efficiencies within this dermal DC subset of 7.6% (±6.1%) and 19.1% (±15.9%), respectively, thus revealing a significantly higher uptake frequency of blebs (P < 0.02). Intradermal delivery of tumor-derived blebs did not affect the T-cell priming and TH-skewing abilities of migratory skin DC. Nevertheless, in contrast to i.d. administration of ACR, the injection of blebs lead to effective cross-presentation of MART-1 to specific CD8+ effector T cells. We conclude that apoptotic bleb-based vaccines delivered through the skin may offer an attractive, and broadly applicable, cancer immunotherapy. Twit Text FOAVip In situ loading of skin dendritic cells with apoptotic bleb-derived antigens for the induction of tumor-directed immunity ????Oncoimmunology http://www.kidney.de/pget.php?&tw=1&pmid=25610730 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25610730 #FOAvip English Wikipedia <ref>{{Cite pmid|25610730}}</ref> In situ loading of skin dendritic cells with apoptotic bleb-derived antigens for the induction of tumor-directed immunity #MMPMID25610730 Ruben JM; Bontkes HJ; Westers TM; Hooijberg E; Ossenkoppele GJ; van de Loosdrecht AA; de Gruijl TD Oncoimmunology 2014[]; 3 (7): ä PMID25610730show ga The generation and loading of dendritic cells (DC) ex-vivo for tumor vaccination purposes is laborious and costly. Direct intradermal (i.d.) administration of tumor-associated antigens could be an attractive alternative approach, provided that efficient uptake and cross-presentation by appropriately activated skin DCs can be achieved. Here, we compare the efficiency of i.d. delivery of relatively small apoptotic blebs (diameter ?0.1?1 ?m) derived from MART-1 transduced acute myeloid leukemia (AML) HL60 cells, to that of larger apoptotic cell remnants (ACR; 2?10 ?m) in a physiologically highly relevant human skin explant model. Injection of either fluorescently-labelled ACRs or blebs alone did not affect the number or distribution of migrated DC subsets from skin biopsies after 48 hours, but resulted in a general up-regulation of the co-stimulatory molecules CD83 and CD86 on skin DCs that had ingested apoptotic material. We have previously shown that i.d. administration of GM-CSF and IL-4 resulted in preferential migration of a mature and highly T cell-stimulatory CD11hiCD1a+CD14? dermal DC subset. Here, we found that co-injection of GM-CSF and IL-4 together with either ACRs or blebs resulted in uptake efficiencies within this dermal DC subset of 7.6% (±6.1%) and 19.1% (±15.9%), respectively, thus revealing a significantly higher uptake frequency of blebs (P < 0.02). Intradermal delivery of tumor-derived blebs did not affect the T-cell priming and TH-skewing abilities of migratory skin DC. Nevertheless, in contrast to i.d. administration of ACR, the injection of blebs lead to effective cross-presentation of MART-1 to specific CD8+ effector T cells. We conclude that apoptotic bleb-based vaccines delivered through the skin may offer an attractive, and broadly applicable, cancer immunotherapy. äIn situ loading of skin dendritic cells with apoptotic bleb-derived an(epmc).pdf DeepDyve Pubget Overpricing