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. 2023 Apr 27;13:1157345. doi: 10.3389/fonc.2023.1157345

Figure 2.

Figure 2

Mechanisms of Treg-mediated immunosuppression in TME. (A) Tregs inhibit the function of APCs and Teffs through immune checkpoints. CTLA4 is highly expressed on Tregs, which binds to CD80/86 on APCs, reduces CD80/86 expressed by APCs through trans-endocytosis, and inhibits the activation of T cells by APCs. (B) Tregs secrete immunomodulatory cytokines and cytotoxic molecules. Tregs directly inhibit the activation of Teffs, NK cells and APCs by secreting immunosuppressive cytokines such as IL-35, IL-10 and TGF-β. Moreover, Tregs can kill immune cells by directly secreting perforin and granzyme, leading to cell apoptosis. (C) Tregs interfere with Teff metabolism. CD39 converts extracellular ATP to generate AMP, which is then cleaved by CD73 to produce immunosuppressive molecular adenosine. Adenosine binds to receptors (A2A or A2B) on the surface of Teffs, APCs and NK cells, resulting in their immunosuppression. CTLA4 induces IDO production by APCs, which can oxidize tryptophan to kynurenine. Tryptophan is an essential amino acid for maintaining T cell activation. (D) Co-inhibition and co-stimulation molecules expressed by Tregs and their ligands. Tregs express a range of co-inhibition molecules of immune checkpoints (CTLA4, PD-1, LAG3, TIM3, and TIGIT) and co-stimulation molecules of Ig superfamily (CD28 and ICOS) as well as TNFR superfamily (OX40, GITR, CD27, 4-1BB, and TNFR2) on the surface.