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Title: An investigation into the induction of tumour cell apoptosis by dsRNA : a pro-inflammatory event?
Author: Lowe, Katie
ISNI:       0000 0004 2730 0329
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2012
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Dendritic cells (DCs) exhibit the capacity to recognise and phagocytose dying cells and invading pathogens and to present antigens from this internalised material on their surface. The recognition of these antigens by T cells can induce specific cytotoxic responses against other cells expressing the same antigen. These characteristics suggest the potential for DCs to be used a Cancer vaccine, due to their ability to stimulate an immune response against tumour cells. To ensure that cytotoxicity, rather than tolerance to the presented antigens is induced, co- stimulatory molecule expression on a DC is necessary. These molecules provide additional signals to T cells to ensure that only antigens presented in the appropriate environment are capable of inducing cytotoxic responses. This thesis investigates the hypothesis that poly (I:C), a synthetic dsRNA analogue, may induce an inflammatory form of apoptosis, releasing tumour antigens and inflammatory mediators capable of maturing DCs, for use as a Cancer vaccine. It has previously been shown that the administration of poly (I:C) induces apoptosis and the release of inflammatory cytokines in intestinal epithelial cells'. Results presented here demonstrate apoptosis, cytokine release and the up regulation of mRNA encoding several inflammatory factors in poly (I:C) treated tumour cells. Internalisation of apoptotic cells by DCs is shown and DCs cultured in supernatants from poly (I:C) treated tumour cells express co-stimulatory and MHC molecules, indicating their potential to stimulate T cells. Results indicate that poly (I:C) treated tumour cells may provide a more efficient method for loading DCs with antigens and inducing DC maturation than the loading of DCs with irradiated tumour material
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available