CD47: Beyond an immune checkpoint in cancer treatment

Biochim Biophys Acta Rev Cancer. 2022 Sep;1877(5):188771. doi: 10.1016/j.bbcan.2022.188771. Epub 2022 Aug 2.

Abstract

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.

Keywords: CD47; Cancer treatment; Cell function; Integrin activation; Target.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD47 Antigen*
  • Caspases / therapeutic use
  • Humans
  • Integrins / therapeutic use
  • Ligands
  • Neoplasms* / pathology
  • Retrospective Studies
  • Thrombospondin 1 / genetics
  • Thrombospondin 1 / therapeutic use

Substances

  • CD47 Antigen
  • CD47 protein, human
  • Integrins
  • Ligands
  • Thrombospondin 1
  • Caspases