Study of immunomics and immune regulation in ovarian cancer
File(s)
Author(s)
Abdul Aziz, Nor Haslinda
Type
Thesis
Abstract
Immunological suppression and regulation may be involved in tumour progression in many cancers. An integrated study has been carried out with regard to the protein expression of immune surface markers, soluble cytokines as well as the functional analysis of immune cells and their relationship to ovarian cancer and its prognosis. Peripheral blood, ascites, and tumour tissues were collected from patients with untreated ovarian cancers and benign ovarian tumours. Peripheral Blood Mononuclear Cells (PBMCs) from healthy women were used as a control. The immune cells that had been isolated for phenotypic analysis were analysed for immune surface and activation marker expressions using flow cytometry. Ovarian cancer tissues were used for immunohistochemistry (IHC) and for tissue RNA extraction to screen immune-related genes by quantitative real time PCR (qRT-PCR). Functional and enzymatic assays were performed to further characterise the regulatory and inhibitory molecules in the patients‟ PBMCs and ascites. It was found that the expression of regulatory T cells and T cell associated programmed death-1 molecule (PD-1) was significantly upregulated in cancer patients on the T cells. The programmed death ligand-1 (PD-L1) expression on monocytes from the patients‟ PBMCs and ascites was observed to have significantly increased in patients with ovarian cancer compared to women with benign diseases. From the functional results, it was hypothesised that PD-L1 may be involved in T cell dysfunction in ovarian cancer. The PBMCs, ascites, and tissues from ovarian cancer patients were also used to study the expression and potential role of immunomodulatory enzymes such as indoleamine 2,3-dioxygenase (IDO) and arginase in ovarian cancer.
Version
Open Access
Date Issued
2013-03
Date Awarded
2014-02
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Ghaem-Maghami, Sadaf
Sponsor
Malaysia
Publisher Department
Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)