**2.2 Programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitor**

PD-1 is also an immune receptor involved in downregulating T-cell response. PD-1 regulates T-cell activation by binding to two ligands (PD-L1 and PD-L2). Cancer tumor cells can block antitumor host responses by upregulating PD-1 ligands. PD-1 has similar effects on T-cells as CTLA-4 but differs in its timing of downregulation and the anatomic location of immune inhibition [3]. PD-1 is more expressed on activated T-cells, B-cells, and myeloid cells compared to CTLA-4 [2, 3, 11]. While CTLA-4 functions during the priming phase of T-cell activation, PD-1 functions during the effector phase, predominantly within peripheral tissues [3, 6]. Chronic antigen exposure, as it occurs in cancer, can lead to an excess PD-1 expression on Tcells, leading to a state of "exhaustion" that can be partially reversible by PD-1 pathway blockade [6]. By inhibiting PD-1 pathway with either antibody to the receptor or its ligands, we can increase antitumor activity. There are currently three PD-1 inhibitor medications approved by the FDA (Nivolumab, Pembrolizumab, and Cemiplimab) and three anti-PD-L1 (Avelumab, Durvalumab, and Atezolizumab).
