Date of Award
Clr-b, E0771, MDSCs, MMTV-PyVT; Natural killer cells, NKR-P1B
Natural killer (NK) cells are large, granular, and cytotoxic innate lymphocytes which do not require prior antigenic exposure to target cancerous and virally infected cells. NK cells possess activating and inhibitory receptors which may activate or inhibit NK cell activity, respectively. In mice, the inhibitory NKR-P1B receptor on NK cells recognizes the C-type lectin-related protein-b (Clr-b) ligand expressed on most autologous cells but downregulated on many tumour cell lines. In B cell lymphoma models, the disruption of NKR-P1B:Clr-b interaction results in delayed tumour development and progression, suggesting that blockage of inhibitory signals from NKR-P1B augments NK cell activity against lymphoma cells. The goal of our research is to evaluate the role of NKR-P1B:Clr-b interaction in a solid tumour model, namely, breast cancer. We used a E0771 cell-induced mammary tumour model to evaluate mammary tumour growth, and the activity of tumour-infiltrating NK cells in NKR-P1B-deficient and WT mice. When we compared tumour onset and development of Nkr1b-/- (KO) versus Nkrp1b+/+ (WT) MMTV-PyVT mice, we found that the knockout mice develop tumours earlier than their wildtype counterparts. We also found that the phenotypes of tumour-infiltrating lymphocytes of WT vs. KO MMTV-PyVT mice differed. When we looked at infiltration of Clr-b-expressing myeloid-derived suppressor cell (MDSC) into these tumours, we found that infiltration of MDSCs into tumours of Nkrp1b-/- mice is greater than WT mice. These findings in mice are significant because they reveal the role of NKR-P1B:Clr-b interactions in NK cell-mediated immunosurveillance of mammary tumours.
Al Olabi, Raghd, "Exploring the role of NKR-P1B:Clr-b interaction in mouse mammary tumour immunosurveillance" (2021). Electronic Theses and Dissertations. 8753.