CTLA-4 (Cytotoxic T-lymphocyte associated protein 4), also referred to CD152, Celiac disease 3, CD, CELIAC3, or GSE, is a 24.7 kDa T cell surface protein with an essential role in downregulation of immune responses. This protein with 223 amino acids encoded by the CTLA4 gene located at the chromosome 2q33.2. It belongs to the immunoglobulin (Ig) gene superfamily and as the first immune checkpoint receptor targeted in clinic. CTLA-4 is exclusively expressed in T lymphocytes, where it mainly regulates the abundance of the early phases of T-cell activation. CTLA4, homologous to the CD28 molecule, both are ligands binding co-stimulatory molecules, CD80 and CD86. But in contrast to CD28, it is a negative feedback signal for T cell activation. PD-1 or PDCD1 (Programmed cell death 1), also known as CD279, is a cell surface receptor expressed on T cells and pro-B cells, which was firstly isolated from a murine T cell hybridoma and a hematopoietic progenitor cell line in 1992. It is an inducible immune modulatory receptor and belongs to a member of the CD28 receptor family. The expression of PD-1 is significantly involved in programmed cell death of lymphocytes. PD-1 has two ligands that are PD-L1 (B7-H1 or CD274) and PD-L2 (B7-DC or CD273). Upon their interactions, PD-1 plays an active role in negative regulation of T cell responses to antigen stimulation and maintaining peripheral tolerance. Thus, it is regarded as an important immune checkpoint for therapeutic antibodies against cancers.