T cell signalling in patients with colorectal cancer
T lymphocytes (T cells) are essential for mediating an effector response against tumours. High infiltrates of T cells in the tumour from colorectal cancer (CRC) patients are associated with positive patient outcomes, indicating their importance in the anti-tumour response in colorectal cancer. The survival and proliferation of T cell depends on the gamma chain family of cytokines, namely, interleukin (IL)-2, IL-7 and IL-15. Therefore, understanding the ability of T cells to respond to signals from these cytokines in cancer patients is essential. Phosphoflow cytometry is a method used to detect activation of signalling pathways by measuring downstream phosphorylation events. The aim of this study was to optimise the phosphoflow cytometry technique and use it to measure signal transducer and activator of transcription (STAT) 5 phosphorylation in T cells from patients with CRC and healthy controls in response to IL-2, IL-7, and IL-15 stimulation. This study found there was no significant difference in signalling through STAT5 phosphorylation in T cells from the blood of colorectal cancer patients compared to healthy controls, and in colorectal tumour tissue compared to non-tumour bowel tissue. However, although no significant differences in signalling were observed, the expression of the surface receptors CD127 and CD122 on CD4+ tumour infiltrating T cells was significantly decreased and increased, respectively, indicating that there may be downstream signalling abnormalities in the T cells. However, these results are preliminary and will need to be validated in a larger cohort of patients.
Advisor: Kemp, Roslyn; McCall, John
Degree Name: Master of Science
Degree Discipline: Microbiology and Immunology
Publisher: University of Otago
Keywords: Immunology; colorectal; cancer; immune; signalling; phosphoflow
Research Type: Thesis