Date of Award

10-1-2021

Publication Type

Thesis

Degree Name

M.Sc.

Department

Biological Sciences

Keywords

Breast cancer, Immunosurveillance, Murine, Natural killer, NK, NKR-P1B

Supervisor

M.M. Rahim

Supervisor

T. Noel

Rights

info:eu-repo/semantics/openAccess

Abstract

Natural killer (NK) cells are lymphocytes of the innate immune system which do not require prior priming to target infected or altered-self cells, such as tumour cells. The basic functions of NK cells include cytotoxicity and cytokine production. These cells possess numerous activating and inhibitory receptors which regulate their function based on a signalling balance. In mice, NK cells possess NKR-P1B inhibitory receptors which recognize the C-type lectin-related protein-b (Clr-b) ligand. This ligand is present on healthy self cells and may be used by cancer cells to evade NK cell effector functions. The disruption of the NKR-P1B:Clr-b axis has been previously shown to delay tumour onset and progression in a B cell lymphoma model, indicative of cancer immunoevasion by means of this inhibitory axis. This research aimed to assess the role of the NKR- P1B:Clr-b axis in mammary tumour immunosurveillance. E0771 mammary adenocarcinoma induced-tumours which were Clr-b-sufficient and -deficient were used as a tumour model to evaluate mammary tumour onset and growth, as well as tumour-infiltrating NK (TINK) cell phenotype in WT and NKR-P1B deficient (Nkrp1b-/-) B6 mice. Nkrp1b-/- mice were found to have a delayed growth and development of mammary tumours. TINKs of Nkrp1b-/- mice also appeared to possess more of an exhausted phenotype in comparison to their WT counterparts. The findings indicate that the NKR-P1B:Clr-b axis plays a role in NK cell- mediated immunosurveillance of mammary tumours, while regulating NK cell exhaustion in tumours.

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