Targeting regulatory T cells in anti-PD-1/PD-L1 cancer immunotherapy

The programmed death (PD)-1/PD-ligand (PD-L) pathway and regulatory T cells (Tregs) are essential for the maintenance of immune tolerance. Their activation in the tumour microenvironment contributes to the evasion of the transformed cells from the immune surveillance and the suppression of an antitumour immune response. Therefore, PD-1/PD-L1 and Tregs are important targets for cancer immunotherapy. Our review focuses on the current role of the PD-1/PD-L1 axis in Treg development and function in the tumour microenvironment. We also discuss combination therapy with PD-1/PD-L1 inhibitors and Treg-modulating agents affecting the adenosinergic pathway, TGF-β signalling, immune checkpoints and other approaches to downregulation of Tregs.