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 (Treg ) 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 Treg 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 Treg cells should be crucial to improving the treatment outcomes of cancer immunotherapy. Several clinical studies directly or indirectly targeting Treg cells in combination with immune checkpoint inhibitors are ongoing or being planned. Understanding the characteristics and roles of Treg cells in cancer settings could make disease-specific Treg -targeted therapy more efficacious and reduce the incidence of immune-related adverse effects mediated by Treg cell inhibition.