Date of Award
9-20-2024
Publication Type
Thesis
Degree Name
M.Sc.
Department
Biological Sciences
Keywords
Cancer immunoevasion;Cancer immunosurveillance;NK cell;NK cell receptors
Supervisor
Munir Rahim
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Abstract
Natural killer (NK) cells are innate lymphocytes that respond to diseased cells via two effector functions: direct cytotoxicity and release of immunomodulatory cytokines. Target cell recognition is mediated by a signaling balance from activating and inhibitory receptors, which recognize target cell ligands. The inhibitory NKR-P1B receptor on mouse NK cells recognizes C-type lectin-related protein-b (Clr-b) and plays an important role in “missing-self” recognition of cells lacking Clr-b and in cancer immunosurveillance. Here, we describe immunoevasion via NKR-P1B:Clr-b interactions in breast cancer. In mammary tumours induced by implantation of E0771 mammary adenocarcinoma cells into the mammary fat pad of female mice, both tumour cells and tumour-infiltrating lymphocytes (TILs) express Clr-b. Using E0771 and Clr-b-deficient (Clrb‒/‒) E0771, we induced mammary tumours in wild-type (WT), NKR-P1B-deficient (Nkrp1b‒/‒), and Clr-b-deficient (Clrb‒/‒) mice to study cancer immunoevasion via NKR-P1B:Clr-b interactions involving tumour cells and TILs. Tumours grew slower, and fewer Nkrp1b‒/‒ mice developed mammary tumours compared to WT and Clrb‒/‒ mice. Conversely, adoptive transfer of Nkrp1b‒/‒, but not WT, NK cells controlled tumour growth in WT mice. Analysis of TILs revealed higher frequencies of PD-1+ and Tim-3+ effector NK cells in mammary tumours from Nkrp1b‒/‒ compared to WT and Clrb‒/‒ mice, indicating higher activation. In vitro, E0771 cells induce activation and proliferation more in Nkrp1b‒/‒ than WT NK cells. These results indicate that Clr-b expression in both tumour cells and TILs can contribute to immunoevasion by modulating NK cell responses via NKR-P1B receptor.
Recommended Citation
Alnajm, Karla, "The role of NKR-P1B:Clr-b interactions in regulating natural killer cell homeostasis in murine mammary tumours" (2024). Electronic Theses and Dissertations. 9391.
https://scholar.uwindsor.ca/etd/9391