Regulatory T cells: a potential target in cancer immunotherapy

Cancer immunotherapy involving blockade of immune checkpoint molecules, such as CTLA-4 and PD-1, has shown remarkable clinical success across several types of malignancies. However, a fraction of patients experience disease progression after treatment; thus, exploring resistant mechanisms for immune checkpoint inhibitors and improving their treatment outcome with additional modalities are of great importance. CD4⁺ regulatory T (T_reg ) cells characterized by expression of the master regulatory transcription factor FOXP3 are a highly immune-suppressive subset of CD4⁺ T cells that maintain immune homeostasis. Several preclinical and clinical studies suggest that T_reg cells hamper immune surveillance against cancer in healthy individuals, prevent the development of effective antitumor immunity in tumor-bearing patients, and promote tumor progression. Therefore, targeting T_reg cells should be crucial to improving the treatment outcomes of cancer immunotherapy. Several clinical studies directly or indirectly targeting T_reg cells in combination with immune checkpoint inhibitors are ongoing or being planned. Understanding the characteristics and roles of T_reg cells in cancer settings could make disease-specific T_reg -targeted therapy more efficacious and reduce the incidence of immune-related adverse effects mediated by T_reg cell inhibition.