Regulatory T Cell Trafficking to the Gut during Colitis-associated Colon Cancer

Chronic inflammation of the colon, as it occurs during ulcerative colitis (UC), prevalently predisposes the tissue to colitis-associated colon cancer (CAC) formation. Although the detailed etiology of UC is poorly understood, regulatory T cells (Tregs) are considered to play a key role in restoring homeostasis during inflammation. However, these suppressive properties might as well be beneficial for tumor progression. We recently identified that the development of CAC is associated with a significant increase in Treg numbers in colonic tumors. Furthermore, depletion of Tregs improved the cytotoxic CD8 T cell response, resulting in reduced tumor growth. Based on these results, this present study now focusses on the migration of Tregs during CAC. We identified a differential gene expression pattern of tumor-infiltrating Tregs and a mainly unmethylated foxp3-TSDR, providing evidence that tumor-infiltrating Tregs are mostly thymus-derived. Moreover, blocking the emigration of Tregs from the mesenteric lymph nodes, led to a reduced number of tumor-infiltrating Tregs, resulting in diminished tumor growth. Therefore we assume that Tregs are rather not induced during CAC formation, but are more likely to have tumor prone migration behaviour. In future experiments we will dissect whether targeting tumor-specific homing molecules will allow us to modulate immune responses during CAC.