Immune activity during progression of human colorectal cancer

Costa Bento, Diana Filipa 2016. Immune activity during progression of human colorectal cancer. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Colorectal cancer (CRC) patients survive and stay free of disease for longer after surgery if their primary tumours were infiltrated with an increased density of T cells. Studies of breast tumours and melanoma have also shown that the presence of specialised blood vessels named high endothelial venules (HEVs), within tumours are associated with a high density of infiltrating T cells and a positive prognosis. It is therefore possible, that presence of HEVs within CRC is associated with a high density of infiltrating T cells and a good patient outcome. To test this hypothesis, primary tumours, resected from sixty-two CRC patients were analysed for the presence of HEVs. These were studied with respect to the numbers and distribution of intra-tumoural T cells as well as tumour stage and patient survival. The results showed that HEV developed in response to CRC but were found within the extra-tumoural area and not the tumour mass. HEVs were also always present within a concentration of T and B cells, namely lymphoid aggregates which resemble ectopic lymphoid structures (ELS). These ELS were associated with more advanced disease and hence did not necessarily identify patients with a better prognosis. Recent studies have suggested that the type of T cells infiltrating the tumours is a determinant for patient outcome indicating that not all T cells confer benefit. IL-17A producing T cells are thought to drive CRC development. Moreover, our laboratory has previously shown that detection of a CEA (Carcinoembryonic antigen)-specific T cell response by in vitro secretion of IFN-γ is associated with tumour recurrence whereas the opposite is true for the 5T4 tumour antigen. This study therefore set out to determine whether IL-17A producing T cells are present at higher frequencies in CRC compared to normal bowel and whether IL-17Aproducing T cells are CEA-specific. The experiments revealed that IL-17A-producing T cells are present at a higher frequency within CRCs, but the prevalence of Th17 responses specific for 5T4 was slightly higher than for CEA, implying that IL-17A secretion by CEA-specific T cells was not responsible for the tumour recurrence. Tumours from CEA-responsive patients were less immunogenic than those from CEA non-responsive patients reflecting the aggressiveness of the tumour.

Item Type:	Thesis (PhD)
Date Type:	Publication
Status:	Unpublished
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Date of First Compliant Deposit:	20 December 2016
Last Modified:	12 Jun 2019 02:55
URI:	https://orca.cardiff.ac.uk/id/eprint/96996

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