Regulatory T cells in cancer immunosuppression - implications for anticancer therapy

Abstract

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.