CD47: Beyond an immune checkpoint in cancer treatment

• Published in: Biochimica et biophysica acta. Reviews on cancer 2022-09, Vol.1877 (5), p.188771-188771, Article 188771
• Main Authors: Bian, Hui-Ting, Shen, Yi-Wen, Zhou, Yu-Dong, Nagle, Dale G., Guan, Ying-Yun, Zhang, Wei-Dong, Luan, Xin
• Format: Article
• Language: English
• Subjects: Cancer treatment; CD47; Cell function; Integrin activation; Target
• ISSN: 0304-419X; 1879-2561
• DOI: 10.1016/j.bbcan.2022.188771

The transmembrane protein, CD47, is recognized as an important innate immune checkpoint, and CD47-targeted drugs have been in development with the aim of inhibiting the interaction between CD47 and the regulatory glycoprotein SIRPα, for antitumor immunotherapy. Further, CD47 mediates other essential functions such as cell proliferation, caspase-independent cell death (CICD), angiogenesis and other integrin-activation-dependent cell phenotypic responses when bound to thrombospondin-1 (TSP-1) or other ligands. Mounting strategies that target CD47 have been developed in pre-clinical and clinical trials, including antibodies, small molecules, siRNAs, and peptides, and some of them have shown great promise in cancer treatment. Herein, the authors endeavor to provide a retrospective of ligand-mediated CD47 regulatory mechanisms, their roles in controlling antitumor intercellular and intracellular signal transduction, and an overview of CD47-targetd drug design. •CD47 induces integrin activation in direct and indirect manners through binding with different ligands.•CD47 functions through forming ternary complex with Gi protein and integrin.•Cell phenotype changing such as apoptosis induced by CD47 is selective for tumor cells.•Antibodies inducing apoptosis and innate immunity recovery is promising in cancer treatment.