Molecular Pathways: Activating T Cells after Cancer Cell Phagocytosis from Blockade of CD47 "Don't Eat Me" Signals

Clin Cancer Res. 2015 Aug 15;21(16):3597-601. doi: 10.1158/1078-0432.CCR-14-2520. Epub 2015 Jun 26.


Recent advances with immunotherapy agents for the treatment of cancer have provided remarkable, and in some cases, curative results. Our laboratory has identified CD47 as an important "don't eat me" signal expressed on malignant cells. Blockade of the CD47:SIRP-α axis between tumor cells and innate immune cells (monocytes, macrophages, and dendritic cells) increases tumor cell phagocytosis in both solid tumors (including, but not limited to, bladder, breast, colon, lung, and pancreatic) and hematologic malignancies. These phagocytic innate cells are also professional antigen-presenting cells (APC), providing a link from innate to adaptive antitumor immunity. Preliminary studies have demonstrated that APCs present antigens from phagocytosed tumor cells, causing T-cell activation. Therefore, agents that block the CD47:SIRP-α engagement are attractive therapeutic targets as a monotherapy or in combination with additional immune-modulating agents for activating antitumor T cells in vivo.

Publication types

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

MeSH terms

  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology
  • Antigens, Differentiation / genetics*
  • Antigens, Differentiation / immunology
  • CD47 Antigen / drug effects
  • CD47 Antigen / genetics*
  • CD47 Antigen / immunology
  • Cytophagocytosis / drug effects
  • Cytophagocytosis / immunology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Humans
  • Immunity, Innate / drug effects*
  • Immunotherapy
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Receptors, Immunologic / genetics*
  • Receptors, Immunologic / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology


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