Immune activity during progression of human colorectal cancer

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