Inhibitory Receptor Expression by T Cells in Colorectal Tumours
|dc.contributor.author||Leman, Julia Kathleen Hayward|
|dc.identifier.citation||Leman, J. K. H. (2019). Inhibitory Receptor Expression by T Cells in Colorectal Tumours (Thesis, Master of Science). University of Otago. Retrieved from http://hdl.handle.net/10523/9293||en|
|dc.description.abstract||Inhibitory receptor (iR) expression is a hallmark of T cell dysfunction. In situations of chronic antigen exposure, such as in a tumour, antigen-specific T cells undergo a shift in programming, which makes them more tolerogenic and less able to produce cytokines, which can result in a dampened anti-tumour immune response. iRs are upregulated during this process, and can transduce signals which inhibit the intracellular signalling required for T cell receptor (TCR)-mediated activation. Targeting iRs using checkpoint blockade therapy can enhance the anti-tumour immune response. However, iRs are also expressed upon activation, and by regulatory T cells (Tregs), and so are expressed by effector and suppressive T cells as well as dysfunctional ones. T cells expressing inhibitory receptors are found at a high frequency in colorectal tumours, yet checkpoint blockade therapy is not an effective treatment for most colorectal cancer (CRC) patients. The aim of my research was to investigate the relationship between iR expression and cytokine production in T cells isolated from CRC patient tumours, and in T cells which were chronically stimulated in vitro. I identified phenotypes of iR-expressing T cell populations from tumours and from in vitro stimulations using mass cytometry and clustering analyses. I found that iR- expressing T cells isolated from CRC tumours or stimulated in vitro were not deficient in cytokine production. I also found that iRs are expressed by populations of effector Tregs (eTregs) that are enriched in colorectal tumours, which produced inflammatory and suppressive cytokines ex vivo. These data suggest that T cells are activated in CRC tumours and upregulate iRs, which drives a suppressive Treg phenotype.|
|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.title||Inhibitory Receptor Expression by T Cells in Colorectal Tumours|
|thesis.degree.discipline||Department of Microbiology and Immunology|
|thesis.degree.name||Master of Science|
|thesis.degree.grantor||University of Otago|
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