Effect of WNT/β-catenin Signalling on T cells in Colorectal Cancer
|dc.contributor.author||Tirados, Justin Factoran|
|dc.identifier.citation||Tirados, J. F. (2019). Effect of WNT/β-catenin Signalling on T cells in Colorectal Cancer (Thesis, Bachelor of Biomedical Sciences with Honours). University of Otago. Retrieved from http://hdl.handle.net/10523/9782||en|
|dc.description.abstract||Worldwide, colorectal cancer (CRC) is the fourth most common cancer and has the second highest mortality rate of any cancer. Only a subset of CRC patients respond to immunotherapies. This lack of response may be due to the diverse immune infiltrates in the CRC tumour microenvironment (TME) and the interaction with other cells and molecules within the TME. The CRC TME is associated with an increase in canonical WNT signalling (β-catenin dependent). WNT signalling promotes tumour cell proliferation and influences the immune component of the TME. An increase in WNT signalling is associated with a decrease in CD8+ T cell recruitment and activation and an increase in regulatory T cell infiltration. WNT signalling triggers de-phosphorylation of β-catenin, its active state, which is translocated into the nucleus, associating with its targets. Without WNT signalling, β-catenin is phosphorylated and degraded in the cytoplasm. I studied the influence of WNT signalling on T cells and hypothesised that an increase in canonical WNT signalling in CRC tumours negatively influences effector T cell functions. I developed a phospho-flow cytometry protocol to detect phosphorylated and de-phosphorylated β-catenin. WNT3a stimulation of T cells from CRC patient peripheral blood mononuclear cells (PBMCs) resulted in a fold-change ratio greater than 1.00. This result meant that more activated β-catenin was detected in WNT3a stimulated T cells than in unstimulated T cells from CRC (PBMCs). This finding was also seen in T cells from healthy control (HC) PBMCs stimulated with WNT3a, albeit at a lower effect compared to T cells from CRC patient PBMCs. T cells from HC PBMCs and from CRC patient PBMCs stimulated with R-spondin3 stimulation did not conclusively show changes in the fold-change ratio. These results demonstrated that WNT signalling may play a role in influencing T cell populations in people with CRC.|
|dc.publisher||University of Otago|
|dc.rights||All items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.|
|dc.subject||Canonical WNT signalling in T cells|
|dc.subject||T cells in CRC|
|dc.subject||T cells in colorectal cancer|
|dc.title||Effect of WNT/β-catenin Signalling on T cells in Colorectal Cancer|
|thesis.degree.discipline||Microbiology and Immunology|
|thesis.degree.name||Bachelor of Biomedical Sciences with Honours|
|thesis.degree.grantor||University of Otago|
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