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 (CTL A-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.