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dc.contributor.advisorKemp, Roslyn
dc.contributor.authorTirados, Justin Factoran
dc.date.available2019-11-10T22:17:58Z
dc.date.copyright2019
dc.identifier.citationTirados, 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/10523/9782en
dc.identifier.urihttp://hdl.handle.net/10523/9782
dc.description.abstractWorldwide, 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.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll 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.subjectT cell
dc.subjectT Cells
dc.subjectWNT signalling
dc.subjectColorectal cancer
dc.subjectCRC
dc.subjectCanonical WNT signalling in T cells
dc.subjectPhosphoflow
dc.subjectPhosphoflow cytomertry
dc.subjectT cells in CRC
dc.subjectT cells in colorectal cancer
dc.titleEffect of WNT/β-catenin Signalling on T cells in Colorectal Cancer
dc.typeThesis
dc.date.updated2019-11-10T21:44:42Z
dc.language.rfc3066en
thesis.degree.disciplineMicrobiology and Immunology
thesis.degree.nameBachelor of Biomedical Sciences with Honours
thesis.degree.grantorUniversity of Otago
thesis.degree.levelHonours
otago.interloanno
otago.openaccessAbstract Only
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