Is CD47 an innate immune checkpoint for tumor evasion?

J Hematol Oncol. 2017 Jan 11;10(1):12. doi: 10.1186/s13045-016-0381-z.

Abstract

Cluster of differentiation 47 (CD47) (also known as integrin-associated protein) is a ubiquitously expressed glycoprotein of the immunoglobulin superfamily that plays a critical role in self-recognition. Various solid and hematologic cancers exploit CD47 expression in order to evade immunological eradication, and its overexpression is clinically correlated with poor prognoses. One essential mechanism behind CD47-mediated immune evasion is that it can interact with signal regulatory protein-alpha (SIRPα) expressed on myeloid cells, causing phosphorylation of the SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and recruitment of Src homology 2 domain-containing tyrosine phosphatases to ultimately result in delivering an anti-phagocytic-"don't eat me"-signal. Given its essential role as a negative checkpoint for innate immunity and subsequent adaptive immunity, CD47-SIRPα axis has been explored as a new target for cancer immunotherapy and its disruption has demonstrated great therapeutic promise. Indeed, CD47 blocking antibodies have been found to decrease primary tumor size and/or metastasis in various pre-clinical models. In this review, we highlight the various functions of CD47, discuss anti-tumor responses generated by both the innate and adaptive immune systems as a consequence of administering anti-CD47 blocking antibody, and finally elaborate on the clinical potential of CD47 blockade. We argue that CD47 is a checkpoint molecule for both innate and adaptive immunity for tumor evasion and is thus a promising target for cancer immunotherapy.

Keywords: CD47; Cancer immunotherapy; Chemotherapy; Clinical trial; Dendritic cell; Macrophage; SIRPα; “Don’t eat me” signal.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Antigens, Differentiation / metabolism
  • CD47 Antigen / immunology*
  • CD47 Antigen / metabolism
  • Humans
  • Immunity, Innate*
  • Immunotherapy / methods
  • Receptors, Immunologic / metabolism
  • Tumor Escape / immunology*

Substances

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