Charalambous, Xenia;
(2022)
Tumour-Priming of Human Natural Killer Cells and the Impact of Tumour Microenvironment in Ovarian Cancer.
Doctoral thesis (Ph.D), UCL (University College London.
Preview |
Text
PhD Thesis Submission-Xenia Charalambous.pdf - Submitted Version Download (4MB) | Preview |
Abstract
Ovarian cancer is the most deadly gynaecological malignancy due to its asymptomatic nature and late detection. First-line treatments include a combination of surgery and chemotherapy. However, the limitation of current treatments results in relapse with chemoresistant residual tumour cells. The presence of immune cells, including the natural killer (NK) cells in the tumour site and malignant ascites, have diverted the focus towards immunotherapy. In this project, NK cells derived from ovarian cancer patients (OCPs) were either isolated from the peripheral blood (PB) or the ascites to compare NK cells in circulation and at the tumour site. Subsequently, the OCP-derived NK cells were compared to NK cells isolated from the PB of healthy volunteered donors (HDs). Herein, is the first time to show a comparison of OCP-derived NK cells and HD-derived NK cells using extensive immunophenotypic panels. Results obtained, revealed an activated phenotype of ascites-derived NK cells via downregulation of CD16 and upregulation of CD2 and CD69 surface markers. However, ascites-derived NK cells exhibited impaired cytotoxic function compared to HD-derived NK cells. Additionally, the downregulation of CD15 levels suggests the potential mechanism behind resistance against NK cell cytotoxicity in ovarian cancer after comparison of the NK cell-resistant SKOV3 and NK cell-sensitive OVCAR3 epithelial ovarian cancer target cells. Moreover, herein, is the first time to show tumour-induced mediated priming of NK cells using the INB16 cell line, a pharmaceutical-grade subline of the original CTV-1 acute monoblastic leukemic cell line against solid tumours, including ovarian cancer. This resulted in successful NK cell activation via downregulation of CD16 and upregulation of CD69 even in the presence of an immunosuppressive low-oxygen (hypoxic) tumour. It is also the first time to demonstrate the interaction between NK cells and ovarian target cells using novel platforms such as the eSIGHT Live Cell Analyser and z-Movi Cell Avidity Analyser.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Tumour-Priming of Human Natural Killer Cells and the Impact of Tumour Microenvironment in Ovarian Cancer |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10154903 |
Archive Staff Only
 |
View Item |
