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Title: An investigation into the role of apolipoprotein E in monocyte differentiation
Author: Kaminska, Elwira
ISNI:       0000 0004 6349 8109
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2017
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Dendritic cells (DCs) are an important target in cancer immunotherapy as they regulate several components of the immune system. Recent DC immunotherapy showed that pre-treatment sera of non-responding melanoma patients had an increased level of apolipoprotein E (ApoE). Here, the effects of ApoE on monocytes and monocyte-derived DCs (moDCs), cells involved in the DC immunotherapy development, were investigated to elucidate if ApoE can skew monocyte differentiation towards macrophages or / and negatively affect functions of moDCs. Methods: Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) of healthy donors. Monocyte ability to activate T cells was measured using ELISpot. Gene profile of monocytes cultured with ApoE was analysed using Illumina® TotalPrep™-96 RNA Amplification kit. MoDCs and macrophage-like cells were differentiated from monocyte and their phenotypes were assessed by flow cytometry. Cytokine productions were measured using ELISA and LUMINEX assays. CD4+ T cell proliferation was measured using [3H]-thymidine incorporation assay. Results: In monocytes, ApoE inhibited the MHC class II expression, however, it did not affect monocyte ability to activate T cells. ApoE did not skew monocyte differentiation from moDCs to macrophage-like cells. MoDCs generated in the presence of ApoE (ApoE/moDCs) showed similar ability to induce proliferation of CD4+ T cells as compared to classic moDCs. Nevertheless, ApoE did alter cytokine profile of monocytes and moDCs cultured with ApoE as well as co-cultured ApoE/moDCs and CD4+ T cells, showing an increase in pro- inflammatory cytokines, including TNF-a and IL-6. Conclusion: Although ApoE did not show to directly impact monocyte differentiation process, it did show immunomodulatory properties by promoting pro-inflammatory cytokine production in monocytes and moDCs. These findings justify the need for further studies to understand the outcomes of increased ApoE serum level in the development of moDCs for immunotherapy and a potential use of ApoE as a biomarker for patient selection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available