Regulatory T cells in cancer: an overview and perspectives on cyclooxygenase-2 and Foxp3 DNA methylation.

Epigenetics has been gaining great attention as a therapeutic target in cancer. The cancer genome usually contains both hyper- and hypo-methylated genes to increase invasion, proliferation and metastasis. These cells not only operate their own growth, but also develop various strategies to escape from immune surveillance, and for this aim, regulatory T (Treg) cells support the cancer-mediated immune suppression. The fate of Treg cells is mainly controlled by DNA methylation within the promoter and intronic regions of Foxp3 gene. Foxp3 transcription factor is involved in the development, differentiation and function of Treg cells. COX-2 is also an epigenetically controlled gene in these processes. This enzyme and its product PGE2 plays essential roles in Treg functionality in cancer. Here, we discuss the effects of DNA methylation on cancer and nTreg cells. We also summarize the mechanisms related with COX-2/PGE2 and Foxp3 on inhibitory function of Treg cells in cancer.