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. Author manuscript; available in PMC: 2019 Nov 17.
Published in final edited form as: Am Soc Clin Oncol Educ Book. 2019 May 17;39:165–174. doi: 10.1200/EDBK_237987

FIGURE 5. Mechanisms of Regulatory T-Cell Suppression in the Tumor Microenvironment.

FIGURE 5.

Regulatory T cells (Tregs) are able to inhibit the function of antigen-presenting cells (APCs) and T effector cells by three main mechanisms. First, Tregs support their own immunosuppressive function by consuming interleukin (IL)-2 (via the IL-2 receptor CD25). Second, Tregs inhibit APCs (via CTLA-4 binding to CD80/CD86) to downregulate costimulatory signals to T effector cells. Third, Tregs directly inhibit T effector cells and APCs with suppressive cytokines (IL-10, IL-35, and transforming growth factor [TGF]-β) or by inducing apoptosis (perforin and granzyme). Alternatively, Tregs can induce suppression by catabolizing adenosine (ADO) from ATP released by apoptotic Tregs under oxidative stress (in the hypoxic and acidic TME) via CD39 and CD79, which binds to ADO A2A receptors (A2AR) on CTLs and APCs to inhibit their function. Abbreviations: TCR, T-cell receptor; MHC, major histocompatibility complex.