The Ovarian Cancer Tumour Microenvironment Modulates Natural Killer Cell Function
dc.contributor.author | Nicolela, Anna Pasternak | |
dc.contributor.copyright-release | Not Applicable | |
dc.contributor.degree | Master of Science | |
dc.contributor.department | Department of Pathology | |
dc.contributor.ethics-approval | Received | |
dc.contributor.external-examiner | Gregory Fairn | |
dc.contributor.manuscripts | Not Applicable | |
dc.contributor.thesis-reader | David Hoskin | |
dc.contributor.thesis-reader | Locke Davenport Huyer | |
dc.contributor.thesis-supervisor | Jeanette Boudreau | |
dc.date.accessioned | 2025-05-29T16:19:25Z | |
dc.date.available | 2025-05-29T16:19:25Z | |
dc.date.defence | 2025-05-13 | |
dc.date.issued | 2025-05-28 | |
dc.description.abstract | Natural killer (NK) cells mediate anti-tumour responses but are inhibited in the high-grade serous carcinoma (HGSC) microenvironment by factors including adenosine (ado) and human leukocyte antigen (HLA)-E/natural killer group 2A (NKG2A) checkpoint. Using flow cytometry, I assessed how ado alters HGSC cells and NK phenotypes. I genotyped HGSC patients for NKG2A polymorphisms and tested their impact on patient outcomes and immune profiles, and I genotyped healthy donors to assess NKG2A polymorphism impact on NK function in vitro. CD16 expression defined two NK subsets with distinct responses to ado; only CD16low NK cells were suppressed by ado-treated targets. NKG2A variant 5 (V5) associated with higher NKG2A expression and stronger responses to HLA-Elow targets. Ado enhanced HLA-E/NKG2A expression and NKG2A polymorphisms dictated ado suppression, revealing a novel link between metabolic and checkpoint inhibition. These findings support dual targeting of ado metabolism and NKG2A to overcome NK suppression in the HGSC microenvironment. | |
dc.identifier.uri | https://hdl.handle.net/10222/85143 | |
dc.language.iso | en | |
dc.subject | ovarian cancer | |
dc.subject | natural killer cells | |
dc.subject | immunotherapy | |
dc.title | The Ovarian Cancer Tumour Microenvironment Modulates Natural Killer Cell Function |