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

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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.

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Acknowledgments

This project was supported by a grant from Cancer Research Center of the Cancer Institute of Iran (Sohrabi Cancer Charity, Grant No: 37652-202-01-97). This project was also financially supported by grant No. 961204 of the Biotechnology Development Council of the Islamic Republic of Iran.

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Authors and Affiliations

  1. Student Research Committee, Department of Medical Biotechnology, Faculty Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Mohammad Gheibi Hayat

  2. Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy

    Vanessa Bianconi & Matteo Pirro

  3. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahmoud R. Jaafari & Mahdi Hatamipour

  4. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahmoud R. Jaafari & Amirhossein Sahebkar

  5. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  6. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  7. Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, P.O. Box: 91779-48564, Mashhad, Iran

    Amirhossein Sahebkar

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  1. Seyed Mohammad Gheibi Hayat
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Hayat, S.M.G., Bianconi, V., Pirro, M. et al. CD47: role in the immune system and application to cancer therapy. Cell Oncol. 43, 19–30 (2020). https://doi.org/10.1007/s13402-019-00469-5

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