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Title: Classical monocytes from patients with pancreatic ductal adenocarcinoma exhibit a significantly altered transcriptome profile compared with healthy volunteers
Author: Cook, Jenny Anne
ISNI:       0000 0004 5355 3485
Awarding Body: Queen Mary, University of London
Current Institution: Queen Mary, University of London
Date of Award: 2014
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Pancreatic Ductal Adenocarcinoma (PDAC) affects approximately 8000 people every year in the UK and is the fifth leading cause of cancer related death. At a molecular level PDAC is characterized by a significant immune infiltrate. Tumour-associated macrophages (TAMs) infiltrate the tumour and contribute to a worse prognosis by promoting growth, metastasis and resistance to chemotherapy. TAMs are derived from circulating ‘classical’ CD14++ CD16- monocytes in the peripheral blood. Current work in murine models suggests targeting monocyte recruitment in PDAC can reduce TAM infiltration and disease burden therefore improving survival. This project aims to identify markers specific to monocytes from PDAC patients and to investigate their biological relevance and potential for therapeutic intervention. Gene expression and metabolomics analysis was carried out on classical CD14++ CD16- monocytes from locally advanced PDAC patients and age matched healthy donors. Transcriptomic profiling revealed a significantly altered gene expression profile in classical monocytes from patients and genes with the highest fold change difference were chosen for validation using qPCR. Validated gene targets were investigated further in vitro and large-scale gene expression analysis from pancreatic tumours assessed. The results from my work demonstrate that the gene expression profile of classical monocytes from PDAC patients is significantly different compared to healthy volunteers. Identification and validation of up-regulated genes and their biological relevance may represent a relevant novel novel biomarker or therapeutic strategyies to target monocytes and myeloid recruitment in cancer.
Supervisor: Not available Sponsor: MedImmune (CIF1RA3R)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Pancreatic Ductal Adenocarcinoma ; cancer related death ; Tumour-associated macrophages ; monocytes ; therapeutic intervention.