PD1 signal transduction pathways in T cells

Abstract

The use of immune checkpoint inhibitors for the treatment of cancer is revolutionizing oncology. Amongst these therapeutic agents, antibodies that block PD-L1/PD1 interactions between cancer cells and T cells are demonstrating high efficacies and low toxicities. Despite all the recent advances, very little is yet known on the molecular intracellular signaling pathways regulated by either PD-L1 or PD1. Here we review the current knowledge on PD1-dependent intracellular signaling pathways, and the consequences of disrupting PD1 signal transduction.

Reviewing vulvar Paget’s disease molecular bases. Looking forward to personalized target therapies: a matter of CHANGE

“…Considering suppression of the immune system as an element of carcinogenesis, we cannot omit considering programmed death ligand-1 (PD-L1), a member of the B7 co-stimulatory/co-inhibitory family expressed in a wide range of cells including tumor cells and antigen-presenting cells. PD-L1-PD-1 interaction interferes with T-cell-mediated signal transduction 32. The increasing interest around immune check-point cellular signaling in oncology is due to the availability of anti-PD-1 and anti-PD-L1 monoclonal antibodies (pembrolizumab, nivolumab, avelumab, atezolizumab, durvalumab), approved by the Food and Drug Administration (FDA) in the treatment of many neoplasms 33.…”

Characterization of Pattern Recognition Receptor Expression and Functionality in Liver Primary Cells and Derived Cell Lines

“…Among tolerogenic mechanisms, there are checkpoint ligand-receptor systems (i.e., PD-1/PD-L1, CTLA-4/B7-1 or 2…) that modulate T-cell receptor-mediated T cell activity [4,5]. This physiologic tolerogenicity represents a sort of Achilles' heel of the liver, which consequently can be the target of various pathogens establishing chronic infections [6].…”

The importance of programmed death ligand 1 gene expression, epidermal growth factor receptor gene mutations and serum epidermal growth factor receptor levels in Turkish non-small cell lung cancer patients

“…[6,7] Recent studies focusing on immunotherapy revealed various immunosuppressive mechanisms including programmed death-1 (PD-1) receptor/programmed death ligand 1 (PD-L1) pathway, a common and complex pathway for escaping from immune system and hence resulting in tumor growth. [8] Programmed death-1 receptor 1 is a transmembrane protein which has two important tyrosine-based motifs in its cytoplasmic domain that implicated in its immunosuppressive effects, expressed in immune cells including T, B and natural killer (NK) cells. [8] On the other hand, PD-L1 is a member of the B7 family of co-stimulatory/ co-inhibitory molecules of antigen presentation and expressed in a wide range of cell types, including cancer cells.…”

“…[8] Programmed death-1 receptor 1 is a transmembrane protein which has two important tyrosine-based motifs in its cytoplasmic domain that implicated in its immunosuppressive effects, expressed in immune cells including T, B and natural killer (NK) cells. [8] On the other hand, PD-L1 is a member of the B7 family of co-stimulatory/ co-inhibitory molecules of antigen presentation and expressed in a wide range of cell types, including cancer cells. [8,9] It was shown that antibodies against both PD-1 and/or PD-L1 which blocks interactions between cancer cells and T-cells benefit NSCLC patients with good survival rates, low toxicity and long lasting responses.…”

“…[8] On the other hand, PD-L1 is a member of the B7 family of co-stimulatory/ co-inhibitory molecules of antigen presentation and expressed in a wide range of cell types, including cancer cells. [8,9] It was shown that antibodies against both PD-1 and/or PD-L1 which blocks interactions between cancer cells and T-cells benefit NSCLC patients with good survival rates, low toxicity and long lasting responses. [9,10] In this study, we aimed to investigate the possible relationships between EGFR gene mutations, serum EGFR levels, PDL-1 gene expression levels and the risks and survivals of resectable NSCLC patients.…”