CD47 is a 47 kDa protein that appears at a position of 70 kDa upon SDS-PAGE due to its hyperglycosylated structure . It consists of:
There are four different spliced isoforms of CD47, with isoform 2 being the most abundantly expressed . CD47 is found on a variety of hematopoietic and non-hematopoietic cells, and its expression level varies depending on the cell type .
CD47 is well-known for its immunoregulatory functions. It acts as a “don’t eat me” signal to prevent phagocytosis by macrophages . This receptor is crucial for maintaining immune system homeostasis by modulating cellular phagocytosis, transmigration of neutrophils, and activation of dendritic cells, T cells, and B cells .
In healthy cells, CD47 prevents phagocytosis, while aged and superfluous cells are removed through phagocytosis due to CD47 down-regulation . This regulatory function was first described in red blood cells but is now known to be widely expressed in other cell types as well .
CD47 is highly expressed in various types of cancer cells, allowing them to escape from the immune system . This makes CD47 a prominent target in cancer therapy. Blocking the interaction between CD47 and SIRPα can enhance cancer cell clearance by macrophages and increase antigen cross-presentation, leading to T-cell priming and an activated adaptive antitumor immune response .
Several strategies have been developed to target CD47 in cancer therapy, including:
Among these, the use of anti-CD47 antibodies is the most advanced approach. These antibodies inhibit the CD47-SIRPα axis, enhancing cancer cell phagocytosis . Combining these antibodies with chemotherapy and immunotherapy has shown promise in improving the survival of cancer patients .