Recent Advances of Tumor Therapy Based on the CD47-SIRPα Axis

Abstract

Cancer is still a major disease that is currently difficult for humans to overcome. When the expression of the cluster of differentiation 47 (CD47) is upregulated, tumor cells interact with the macrophage inhibitory receptor signal regulatory protein α (SIRPα) to transmit the "Don't eat me" signal, thereby avoiding phagocytosis by the macrophages. Therefore, when the CD47-SIRPα axis is inhibited, the macrophages' phagocytic function can be restored and can also exert antitumor effects. This Review mainly introduces recent advances in tumor therapy targeted on the CD47-SIRPα axis, including the antibody and fusion protein, small molecule, gene therapy, cell therapy, and drug delivery system, to inhibit the function of CD47 expressed on tumor cells and promote tumor phagocytosis by macrophages. In addition, this Review also summarizes the current approaches to avoid anemia, a common side effect of CD47-SIRPα inhibitions, and provides ideas for clinical transformation.

Unravelling soluble immune checkpoints in chronic lymphocytic leukemia: Physiological immunomodulators or immune dysfunction

“…In normal tissues, there is a constant balance between inhibition/activation of phagocytosis that is disproportionate in malignant cells, mainly because of the upregulation of CD47. In addition, CD47 interacts with signal regulatory protein α (SIRPα) expressed in myeloid cells (monocytes, macrophages, and DCs), blocking the migration and phagocytosis process of these cell types ( 12 , 16 , 17 , 40 ).…”

“…Also, several studies report that B-CLL cells express signals to inhibit phagocytosis capacity of the macrophages. In fact, high levels of antiphagocytic molecules like PD-L1, major histocompatibility complex I (MHC-I), CD24, and CD47 allow the inhibition of macrophage action and the breaking of immune homeostasis, which leads to the persistence of tumoral cells ( 16 , 17 ).…”

CD47 as a promising therapeutic target in oncology

“…Apart from anemia, issues with thrombocytopenia, hyperbilirubinemia, and neutropenia have also limited the use of anti-CD47. For further reading on this field, we recommend to the curious reader one excellent review by Yuchen W et al (135). The review also high-light recent advances in tumor therapy targeted on the CD47-SIRPa axis and provides ideas for further clinical transformation.…”

“…For further reading on this field, we recommend to the curious reader one excellent review by Yuchen W et al. ( 135 ). The review also high-light recent advances in tumor therapy targeted on the CD47-SIRPα axis and provides ideas for further clinical transformation.…”

Crystal Structure of Human CD47 in Complex with Engineered SIRPα.D1(N80A)

“…Thus, overexpression of CD47 enables tumor cells to evade immune surveillance via the blockade of phagocytic mechanisms [ 1 ]. Meanwhile, macrophages play an important role in the immune system by phagocytosis mediated by various pathways such as phosphatidylserine (PS) extracellular exposure, representing an “eat me” signal for macrophages to activate the phagocytosis [ 2 ]. The CD47–SIRPα axis regulates homeostatic processes by controlling myeloid cell-mediated removal of aging cells, erythrocytes, hematopoietic stem cells and neuronal synapses [ 3 ].…”