Is CD47 an innate immune checkpoint for tumor evasion?

Xiaojuan Liu, Hyunwoo Kwon, Zihai Li, Yang xin Fu

Research output: Contribution to journalReview article

70 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalJournal of Hematology and Oncology
Volume10
Issue number1
DOIs
StatePublished - Jan 11 2017

Keywords

  • "Don't eat me" signal
  • Cancer immunotherapy
  • CD47
  • Chemotherapy
  • Clinical trial
  • Dendritic cell
  • Macrophage
  • SIRPα

ASJC Scopus subject areas

  • Hematology
  • Molecular Biology
  • Oncology
  • Cancer Research

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