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.
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.
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.