[Suppression of tumor antigen-specific T cell immune responses by regulatory T cells]

CD4⁺ CD25⁺ FOXP3⁺ regulatory T cells(Tregs)play important roles in maintaining self-tolerance in vivo by suppressing self antigen- reactive T cells. In the tumor microenvironment, tumor cells produce several chemokines and attract Tregs, resulting in suppression of tumor antigen-specific cytotoxic CD8⁺ T cell activation. Controlling the suppressive function of Tregs to recover anti-tumor immune responses in the tumor microenvironment is critical to improve the efficiency of cancer immunotherapy. Many immune-checkpoint blockade reagents, including antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA- 4), programmed cell death (PD)-1, and PD-L1, have been tested in the clinic and elicit clinical responses in several types of cancers. Importantly, clinical responses in melanoma patients treated with an anti-CTLA-4 antibody were associated with a reduced number of Tregs in the tumor microenvironment. Therefore, in addition to activating or expanding antigen-specific cytotoxic T cells, modulating the number and/or function of Tregs in the tumor microenvironment is the next important challenge in the field of cancer immunotherapy.