CD47 is a five-pass transmembrane protein expressed on all normal cells, as well as in cancer cells. CD47 is used by macrophages to distinguish between self and non-self cells. SIRPalpha expressed on myeloid cells including macrophages, and neuronal cells in the central nervous system, can bind CD47. SIRPalpha cytoplasmic tail can inhibit macrophage phagocytosis towards CD47-expressing cells. Thus, the CD47/SIRPalpha pahtway serves as an innate immune checkpoint. Additionally, CD47 was reported to modulate lymphocyte cell activation and proliferation. CD47 is over-expressed in many types of cancer, and the expression level of CD47 on cancer cells is negatively associated with cancer survival. Monoclonal antibody therapies that can block CD47-SIRPalpha interaction are being actively pursued for clinical applications. In addition to SIRPalpha, CD47 interacts with thrombospondin-1, VEGFR2, FAS, and certain integrins in different contexts, and influences their downstream signaling.
