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Immunoregulatory effects of freeze injured whole tumour cells on human dendritic cells using an in vitro cryotherapy model.
MedLine Citation:
PMID:  20863822     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Tumour cryotherapy has been described as both immunostimulatory and immunoinhibitory in previous studies. However, previous studies have not accurately reproduced the precise conditions of current clinical cryotherapy. The objective of this study is to assess the immunological effects of cryotreated whole tumour cells on dendritic cells (DC) maturation and function using an in vitro model. Prostate cancer cells were cooled using Endocare cryo-system to mimic temperatures achieved during clinical cryotherapy. Human DC were prepared from cluster of differentiation (CD) 14 monocytes and matured with lipopolysaccharide (LPS). Cryotreated cancer cells were added to DC on day 3. On day 7, DC were harvested and phenotyped. Cytokine gene expression was assessed using real time quantitative polymerase chain reaction (RT-PCR). Functional activity of DC was assessed in allogenic mixed lymphocyte reaction (MLR) and the molecular changes using gene microarray technology. There was statistically significant upregulation of costimulatory molecules and maturation markers (CD86, CD83, CD80 and CL II) in DC loaded with cryotreated whole tumour cells compared to both control DC and DC matured with LPS (P<0.001). There was a significant increase in stimulatory cytokines gene expression (IL-2, IL-12, IL-15, IL-18 and IFN-γ). However, IL-10 and TGF-β expression reduced significantly. The effect of different freezing temperature was equal. cDNA microarray analysis showed upregulation of interleukin 1 (IL-1) and cycline dependent kinase inhibitor 1A (CDKN1A (p21) and downregulation of Caspase 8 and BCL2. Overall, our findings suggest that the effect of cryotherapy is generally stimulatory to DC which may enhance anti-tumour effects. Therefore, the combination of cryotherapy and DC vaccine may represent a novel method to increase the efficacy of cryotherapy especially at the peripheral zones of the prostate where cells are exposed to sub-lethal temperature.
Authors:
Mohamed Ismail; Richard Morgan; Kevin Harrington; John Davies; Hardev Pandha
Publication Detail:
Type:  Journal Article     Date:  2010-09-21
Journal Detail:
Title:  Cryobiology     Volume:  61     ISSN:  1090-2392     ISO Abbreviation:  Cryobiology     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0006252     Medline TA:  Cryobiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  268-74     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Postgraduate Medical School, University of Surrey, Guildford, Surrey GU2 7WG, UK.
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