The overall potential of CD47 in cancer immunotherapy: with a focus on gastrointestinal tumors

Expert Rev Anticancer Ther. 2019 Nov;19(11):993-999. doi: 10.1080/14737140.2019.1689820. Epub 2019 Nov 8.

Abstract

Introduction: CD47 is an anti-phagocytic ('don't eat me') signal overexpressed in many malignant diseases. It acts as myeloid immune checkpoint and thus has prognostic and therapeutic implications.Areas covered: This review presents and discusses the currently available data on the prognostic role and therapeutic value of CD47 in gastrointestinal tumors.Expert opinion: CD47 is overexpressed on the great majority of gastrointestinal tumors, cancer stem cells and circulating tumor cells. Overexpression of CD47 usually predicts a negative prognosis and seems to contribute to cancer immune evasion. The inhibition of CD47 has shown impressive results in clinical trials in hematologic malignancies. However, for gastrointestinal tumors only preclinical data is available. Inhibition of this myeloid immune checkpoint may yield great clinical benefit due to the abundance of myeloid effector cells. However, due to the ubiquitous expression of CD47 and the resulting antigen sink, vast amounts of antibody are required in order to reach therapeutic concentrations. QPCTL inhibitors blocking post-translational modification of CD47 protein may be a solution to this problem.

Keywords: CD47; Gastrointestinal cancer; SIRPα; checkpoint inhibition; colorectal cancer; don’t eat me signal; esophageal cancer; macrophages; pancreatic cancer.

Publication types

  • Review

MeSH terms

  • Animals
  • CD47 Antigen / immunology*
  • Gastrointestinal Neoplasms / immunology
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Neoplasms / therapy*
  • Humans
  • Immunotherapy / methods*
  • Neoplastic Cells, Circulating / metabolism
  • Neoplastic Stem Cells / metabolism
  • Prognosis

Substances

  • CD47 Antigen
  • CD47 protein, human