PD‐1/PD‐L1 immune checkpoint: Potential target for cancer therapy

Abstract

Recent studies show that cancer cells are sometimes able to evade the host immunity in the tumor microenvironment. Cancer cells can express high levels of immune inhibitory signaling proteins. One of the most critical checkpoint pathways in this system is a tumor-induced immune suppression (immune checkpoint) mediated by the programmed cell death protein 1 (PD-1) and its ligand, programmed death ligand 1 (PD-L1). PD-1 is highly expressed by activated T cells, B cells, dendritic cells, and natural killer cells, whereas PD-L1 is expressed on several types of tumor cells. Many studies have shown that blocking the interaction between PD-1 and PD-L1 enhances the T-cell response and mediates antitumor activity. In this review, we highlight a brief overview of the molecular and biochemical events that are regulated by the PD-1 and PD-L1 interaction in various cancers.

A pooled analysis of the prognostic value of PD-L1 in melanoma: evidence from 1062 patients

“…Lieping Chen et al identified and cloned the human B7-H1 gene in the year 1999 and found that this molecule could negatively regulate T cell function through the induction of IL-10 [16]. Accumulating evidence shows that PD-L1 plays a central role in the regulation of the immune responses in the tumor microenvironment [50]. PD-L1 binds to PD-1 and inhibits T cell proliferation and its cytokine secretion and leads to apoptosis, anergy, and exhaustion of T cells [51].…”

Basis of PD1/PD-L1 Therapies

“…Next to this, PD-1 ligation alters the metabolic program of activated T cells thereby generating a more oxidative microenvironment [48,49]. PD-1 signaling is well understood and has been recently extensively reviewed [50], while only limited information on PD-L1 signaling is available. However, there exists evidence of a reverse signaling via cross-binding with mAbs.…”

Predictive Role of Computed Tomography Texture Analysis in Patients with Metastatic Urothelial Cancer Treated with Programmed Death-1 and Programmed Death-ligand 1 Inhibitors

“…Together, the role of this pathway is to suppress the activation of T cells, when activated by its circulating ligands, occurring in the context of infection or tumor progression [4,5]. When PD-1 receptors are blocked, T cells initiate an inflammatory response against the tumor [6].…”