Fig. 2

Effects of Tregs on the immune cells. The mechanism mainly includes four aspects:①secreting inhibitory cytokines, including IL-10, TGF-β, IL-35 etc., eg. inhibiting immune function through il-10 and other dependent ways, and Treg can also inhibit CD8+ T cells and DCs through membrane-bound TGF-β, thereby regulating the body‘s anti-tumor immune function. ②killing effector cells by granulase and perforin. Granzyme and perforin are the main molecules that mediate the cytotoxicity of CTL, NK and other cells.③Tregs affect effector cell function by interfering with cell metabolism mainly in the following three ways:(1) Deprivation of IL-2 in the TME, and the growth of Tregs and effector T cells requires the maintenance of IL-2. (2) CD39 and CD73 are nucleases that are constitutionally expressed in human and mouse Tregs. They can hydrolyse extracellular ATP or ADP into AMP and produce Adenosine. Tregs promotes the production of adenosine in the TME by producing the extracellular enzymes CD39 and CD73, and produces inhibitory and anti-proliferative effects by binding to the adenosine receptor A2A on the surface of effector cells. (3) Treg transferred a large number of cAMP to effector T cells through gap junction to interfere with their metabolism. ④Affect the differentiation and proliferation of Tregs by regulating DCs. The Tregs-expressed CTLA-4 was combined with CD80 and CD86 on the surface of DCs to downregulate the synergistic stimulus signal. Lymphocyte activation gene 3 (LAG3) molecules expressed by Tregs can inhibit the expression of MHC II molecules in DCs. DCs tolerance can be induced by the above two methods, and the latter can further induce T cell incapacity by IDOc. ⑤There exist the functional crosstalk between Tregs and MDSCs. Factors produced by both MDSCs and Tregs form positive feedback loops to facilitate the expansion of each population and reinforce the suppressive environment. On the one hand, MDSCs promoted the induction of Tregs through producing molecules including TGF-β, IL10, CD73, and IDO. On the other hand, Tregs can also modulate MDSCs expansion and function through secreting IL-35 and TGF-β. Additionally, cell-surface molecular interactions can promote the function of both MDSC and Tregs, including CD40/CD40L, PD-1/PD-L1, and CD80/CTLA-4