CD47: role in the immune system and application to cancer therapy

Cell Oncol (Dordr). 2020 Feb;43(1):19-30. doi: 10.1007/s13402-019-00469-5. Epub 2019 Aug 14.

Abstract

Background: CD47 is a widely expressed cellular receptor well known for its immunoregulatory functions. By interacting with its ligands, including thrombospondin-1 (TSP-1), signal regulatory protein α (SIRPα), integrins, and SH2-domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1), it modulates cellular phagocytosis by macrophages, transmigration of neutrophils and activation of dendritic cells, T cells and B cells. Ample studies have shown that various types of cancer express high levels of CD47 to escape from the immune system. Based on this observation, CD47 is currently considered as a prominent target in cancer therapy.

Conclusions: Here, we review the role of CD47 in the maintenance of immune system homeostasis. We also depict three emerging CD47-targeting strategies for cancer therapy, including the use of mimicry peptides, antibodies, and gene silencing strategies. Among these approaches, the most advanced one is the use of anti-CD47 antibodies, which enhances cancer cell phagocytosis via inhibition of the CD47-SIRPα axis. These antibodies can also achieve higher anti-cancer efficacies when combined with chemotherapy and immunotherapy and hold promise for improving the survival of patients with cancer.

Keywords: CD47; Efferocytosis; Macrophage; Tumor.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Differentiation / metabolism
  • B-Lymphocytes / immunology*
  • CD47 Antigen / metabolism
  • CD47 Antigen / physiology*
  • CD47 Antigen / therapeutic use
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Humans
  • Integrins / metabolism
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Neutrophils / metabolism
  • Phagocytosis / immunology*
  • Receptors, Immunologic / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*

Substances

  • Antigens, Differentiation
  • CD47 Antigen
  • CD47 protein, human
  • Integrins
  • Receptors, Immunologic
  • SIRPA protein, human