Regulatory T cells (Tregs) are among the most abundant suppressive cells, which infiltrate and accumulate in the tumor microenvironment, leading to tumor escape by inducing anergy and immunosuppression. Their presence has been correlated with
tumor progression, invasiveness and
metastasis. Targeting
tumor-associated Tregs is an effective addition to current
immunotherapy approaches, but it may also trigger
autoimmune diseases. The major limitation of current
therapies targeting Tregs in the tumor microenvironment is the lack of selective targets.
Tumor-infiltrating Tregs express high levels of cell surface molecules associated with T-cell activation, such as CTLA4, PD-1, LAG3, TIGIT, ICOS, and
TNF receptor superfamily members including 4-1BB, OX40, and GITR. Targeting these molecules often attribute to concurrent depletion of antitumor effector T-cell populations. Therefore, novel approaches need to improve the specificity of targeting Tregs in the tumor microenvironment without affecting peripheral Tregs and effector T cells. In this review, we discuss the immunosuppressive mechanisms of
tumor-infiltrating Tregs and the status of antibody-based
immunotherapies targeting Tregs.