PD1 / PDCD1 / CD279, a type 1 transmembrane protein of the Ig superfamily, consists of an extracellular N-terminal IgV-like domain, a transmembrane domain, and a cytoplasmic tail engaging in inhibitory signal transmission. Being expressed on activated immune cell types including T cells, B cells, natural killer (NK) cells, NKT cells, dendritic cells (DCs), macrophages, and host tissues, the expression on effector T cells is associated with constitutive antigen exposure and thus PD1 / PDCD1 / CD279 has become a marker of T cell unresponsiveness or exhaustion.
Immune Checkpoint Targets: PD-L1
PD1 / PDCD1 / CD279 has two known ligands, PD-L1 / B7-H1 / CD274 and PD-L2 / B7-DC / CD273, which belong to B7 family. PD-L1 / B7-H1 / CD274 is the major ligand and expressed on hematopoietic cells including T cells, B cells, DCs, macrophages and mast cells as well as many nonhematopoietic cells including endothelial cells and numerous epithelial cells. PD-L1 / B7-H1 / CD274 is expressed on many tumors including cancers developing in various organs such as head and neck, lung, stomach, colon, pancreas, breast, kidney, bladder, ovary, cervix, as well as melanoma, glioblastoma, multiple myeloma, lymphoma, and various leukemias, thereby inhibits effective anti-tumor immune responses mediated by PD1 / PDCD1 / CD279 -expressed T cells.
Immune Checkpoint Targets: CD27
CD27 is a lymphocyte-specific member of the tumour necrosis factor receptor (TNF-R) family, expression of which is tightly regulated during T-cell ontogeny. Recently, the ligand for CD27 was identified and was shown to be identical to CD70, a novel member of the TNF family. Functional experiments show that the interaction between CD27 and its ligand generates a co-stimulatory signal for T-cell activation.
Immune Checkpoint Background
Immune checkpoint therapies have attracted amounts of attention from scientists who are devoted to cancer treatment. What is immune checkpoint? It is a kind of co-stimulatory and inhibitory signal for regulating the antigen recognition of T cell receptor (TCR) in the process of immune responce. When immune system is attacking pathogens, these immune checkpoint molecules can protect the normal tissues from damage. The cancer cells cleverly escape from immune attack by dysregulating immune checkpoint related proteins. Immune checkpoint therapy relys on functioning immune system with agonists of co-stimulatory signals or antagonists of inhibitory signals. Over these years there are two immune checkpoint receptors that have been actively studied: cytotoxic T‑lymphocyte-associated antigen 4 (CTLA-4 / CD152) and programmed cell death protein 1 (PD1 / PDCD1 / CD279). The corresponding antibodies can inhibit the functioning of the receptors and enhance antitumour immunity. Furthermore, multiple additional immune checkpoints, representing promising targets for anti-cancer therapy are under active development, more therapies based on immune checkpoint for more cancers are on the way to the market.