Programmed cell death protein 1 (PD-1) is also known as CD279 and PDCD1, is a type I membrane protein and is a member of the extended CD28/CTLA-4 family of T cell regulators. PDCD1 is expressed on the surface of activated T cells, B cells, macrophages, myeloid cells and a subset of thymocytes. PD-1 has two ligands, PD-L1 and PD-L2, which are members of the B7 family. PD-L1 is expressed on almost all murine tumor cell lines, including PA1 myeloma, P815 mastocytoma, and B16 melanoma upon treatment with IFN-γ. PD-L2 expression is more restricted and is expressed mainly by DCs and a few tumor lines. PD1 inhibits the T-cell proliferation and production of related cytokines including IL-1, IL-4, IL-10 and IFN-γ by suppressing the activation and transduction of PI3K/AKT pathway. In addition, coligation of PD1 inhibits BCR-mediating signal by dephosphorylating key signal transducer. In vitro, treatment of anti-CD3 stimulated T cells with PD-L1-Ig results in reduced T cell proliferation and IFN-γ secretion. Monoclonal antibodies targeting PD-1 that boost the immune system are being developed for the treatment of cancer.
Non small cell lung cancer (NSCLC), Metastatic melanoma, Head and neck cancer, Advanced melanoma
MERCK SHARP DOHME
Gastric cancer, Colorectal neoplasms, Advanced renal cell carcinoma (RCC), Primary mediastinal B cell lymphoma, Urothelial cancer, Solid tumours, Squamous cell carcinoma of head and neck cancer (SCCHN), Hepatocellular carcinoma (HCC), Microsatellite instability-high cancer, Advanced melanoma, Head and neck cancer, Hodgkin lymphoma, Small cell lung cancer (SCLC), Non small cell lung cancer (NSCLC), Diffuse large B cell lymphoma, Merkel cell carcinoma, Metastatic melanoma, Cervical carcinoma, Melanoma
Gastric adenocarcinoma, Non small cell lung cancer (NSCLC), Diffuse large B cell lymphoma, Renal cell carcinoma, Urothelial cancer, Solid tumours, Squamous cell carcinoma of head and neck cancer (SCCHN), Hodgkin lymphoma, Gastroesophageal junction adenocarcinoma, Melanoma