Tumor cells establish a unique circumstance called tumor microenvironment(TME)suitable for tumor development and progression. One ofthe most important advantages ofTME for tumor cells is immunosuppressive environment such as higher presence ofregulatory T(Treg)cells, which play a central role for establishment and maintenance of immunological selftolerance and homeostasis. CTLA-4 expressed by Treg cells prevents the maturation ofAPCs resulting in suppression ofT -cell activation. Inhibitory cytokines and adenosine produced by Treg cells are also responsible for their suppressive functions. Indeed, high infiltration of Treg cells has been observed in many tumor tissues and is associated with poor clinical outcomes. Treg cells are recruited into tumors via chemokines secreted by tumor cells and immune cells, and further expand in TME. It has recently been shown that the metabolism oftumor cells and infiltrated immune cells in TME is also important component for tumor immunosuppressive environment. Effector T(Teff)cells rely on glycolysis for their proliferation and effector function, whereas Treg cells predominantly employ oxidative phosphorylation for suppressive function. In TME, tumor cells uptake and utilize large amounts ofglucose and glutamine and the concentration ofthose nutrients is much lower than that in normal tissues or peripheral blood. Under low glucose conditions, Teff cells fail to drive glycolysis for their survival and effector function. While the shortage of glutamine causes inhibition of Teff-cell proliferation and cytokines production, it is favorable for Treg cells. High consumption of glucose through glycolysis by tumor cells results in lactate accumulation in TME, resulting in suppression to proliferation and function of Teff cells. By contrast, high lactate level increases Treg cells with suppressive function. Furthermore, adenosine generated by tumor cells and Treg cells is known to impair the function of Teff cells. Together, various factors in TME including the metabolism of tumor cells and infiltrated immune cells allow Treg cells to infiltrate, proliferate and exhibit strong suppressive function, leading to dysfunction of Teff cells.