is facilitated by the binding of the chemokine receptor CCR4, which is expressed on Treg cells, to its ligand CCL22, which is secreted by many types of tumor cells. Treg cell expansion at the site of the tumor could also explain the increased levels of Treg cells. The cytokine, TGF-β, which is commonly produced by tumor cells, is known to induce the differentiation and expansion of Treg cells. Forkhead box protein 3 (FOXP3) as a transcription factor is an essential molecular marker of Treg cells. FOXP3 polymorphism (rs3761548) might be involved in the gastric cancer progression through influencing Treg function and the secretion of immunomodulatory cytokines such as IL-10, IL-35, and TGF-β. In general, the immunosuppression of the tumor microenvironment has largely contributed to the unsuccessful outcomes of many cancer immunotherapy treatments. Depletion of Treg cells in animal models has shown an increased efficacy of immunotherapy treatments, and therefore, many immunotherapy treatments are now incorporating Treg depletion. Molecular characterization Similar to other T cells, regulatory T cells develop in the thymus. The latest research suggests that regulatory T cells are defined by expression of the forkhead family transcription factor FOXP3 (forkhead box p3). Expression of FOXP3 is required for regulatory T cell development and appears to control a genetic program specifying this cell's fate. The large majority of Foxp3-expressing regulatory T cells are found within the major histocompatibility complex (MHC) class II restricted CD4-expressing (CD4+) population and express high levels of the interleukin-2 receptor alpha chain (CD25). In addition to the FOXP3-expressing CD4+ CD25+, there also appears to be a minor population of MHC class I restricted CD8+ FOXP3-expressing regulatory T cells. These FOXP3-expressing CD8+ T cells do not appear to be functional in healthy individuals but are induced in autoimmune disease states by T cell receptor stimulation to suppress IL-17-mediated immune responses. Unlike conventional T cells, regulatory T cells do not produce IL-2 and are therefore anergic at baseline. A number of different methods are employed in research to identify and monitor Treg cells. Originally, high expression of CD25 and CD4 surface markers was used (CD4+CD25+ cells). This is problematic as CD25 is also expressed on non-regulatory T cells in the setting of immune activation such as during an immune response to a pathogen. As defined by CD4 and CD25 expression, regulatory T cells comprise about 5–10% of the mature CD4+ T cell subpopulation in mice and humans, while