Regulatory T cells in cancer immunosuppression — implications for anticancer therapy

Regulatory T (T reg ) cells, an immunosuppressive subset of CD4 + T cells characterized by the expression of the master transcription factor forkhead box protein P3 (FOXP3), are a component of the immune system with essential roles in maintaining self-tolerance. In addition, T reg cells can suppress anticancer immunity, thereby hindering protective immunosurveillance of neoplasia and hampering effective antitumour immune responses in tumour-bearing hosts, thus promoting tumour development and progression. Identification of the factors that are specifically expressed in T reg cells and/or that influence T reg cell homeostasis and function is important to understanding cancer pathogenesis and to identifying therapeutic targets. Immune-checkpoint inhibitors (ICIs) have provided a paradigm shift in the treatment of cancer. Most immune-checkpoint molecules are expressed in T reg cells, but the effects of ICIs on T reg cells, and thus the contributions of these cells to treatment responses, remain unclear. Notably, evidence indicates that ICIs targeting programmed cell death 1 (PD-1) might enhance the immunosuppressive function of T reg cells, whereas cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors might deplete these cells. Thus, although manipulation of T reg cells is a promising anticancer therapeutic strategy, approaches to controlling these cells require further research. Herein, we discuss novel insights into the roles of T reg cells in cancer, which can hopefully be used to develop T reg cell-targeted therapies and facilitate immune precision medicine. Regulatory T (T reg ) cells are implicated in cancer immune evasion and escape and thus contribute to tumour development and progression. In this Review, the authors provide an overview of the phenotypes and roles of T reg cells in the context of cancer and outline potential strategies to target this cell type in anticancer immunotherapy. Key points Regulatory T (T reg ) cells are a subset of CD4 + T cells with immunosuppressive effects through various cellular and humoral mechanisms: cytotoxic T lymphocyte antigen 4 (CTLA-4)-mediated suppression of antigen-presenting cells, consumption of IL-2 and production of immune inhibitory cytokines and molecules. T reg cells can suppress antitumour immunity, thereby hindering immunosurveillance against cancer development in individuals without existing cancer and hampering effective antitumour immune responses in tumour-bearing hosts. T reg cells with an activa