Current Landscape and Future Direction of PD-1/PD-L1 Checkpoint Inhibitors in Cancer Treatment

Immune checkpoints are involved in controlling the activation or inhibition of the immune response and are associated with receptors on the immune cell surface [1]. A type of immunotherapy is represented by Immune Checkpoint Inhibitors (ICIs) which have the function of stimulating the anti-tumor immune response by blocking the cell surface receptors of T lymphocytes [2]. The blockade of PD-1/PD-L1 and CTLA-4 molecules repre sents two of the most promising checkpoint inhibition strategies used in recent years [3]. In particular, PD-1 plays a crucial inhibitory role in the signalling of programmed cell death in response to the T cell-mediated process [4]. It is widely expressed in different types of immune cells within the tumor microenvironment (TME). During the binding of PD-1 to its ligand PD-L1, an inhibitory signal is transmitted resulting in T-cell inhibition and, ultimately, exhaustion [5]. PD-1 acts primarily to limit T cell activity in peripheral tissues in the later stages of tumor progression, unlike CTLA-4 which instead regulates T cell activity in the early stages of tumor growth [6].