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The Ovarian Cancer Tumour Microenvironment Modulates Natural Killer Cell Function

dc.contributor.authorNicolela, Anna Pasternak
dc.contributor.copyright-releaseNot Applicable
dc.contributor.degreeMaster of Science
dc.contributor.departmentDepartment of Pathology
dc.contributor.ethics-approvalReceived
dc.contributor.external-examinerGregory Fairn
dc.contributor.manuscriptsNot Applicable
dc.contributor.thesis-readerDavid Hoskin
dc.contributor.thesis-readerLocke Davenport Huyer
dc.contributor.thesis-supervisorJeanette Boudreau
dc.date.accessioned2025-05-29T16:19:25Z
dc.date.available2025-05-29T16:19:25Z
dc.date.defence2025-05-13
dc.date.issued2025-05-28
dc.description.abstractNatural 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.urihttps://hdl.handle.net/10222/85143
dc.language.isoen
dc.subjectovarian cancer
dc.subjectnatural killer cells
dc.subjectimmunotherapy
dc.titleThe Ovarian Cancer Tumour Microenvironment Modulates Natural Killer Cell Function

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