CD47:

Regulation of cellular phagocytosis in

cancer, inflammation & neurobiology
CD47 is a cell surface ‘don’t eat me’ signal that has been shown to be important
in detection and evasion of cancer cells, inflammation, neuronal pruning and other
pathophysiological processes. Healthy cells express CD47 to avoid attack by
phagocytes, or in the case of neurons, the level of CD47 expression can modulate
the ‘pruning’ of injured cells by microglia. CD47 is commonly overexpressed in
tumor cells and prevents their engulfment, resulting in unchecked tumor growth.
Blocking CD47 allows tumor cells to be recognized by phagocytes and this cell-cell
interaction initiates a cascade of events resulting in tumor cell destruction.
As such CD47 is an attractive target for the development of novel therapeutics.

homeostasis
Within normal tissue, phagocytosis
SIRPα of healthy cells by macrophages
is supressed by the presence of
CD47 Macrophage cell surface ‘don't eat me’ signals,
Viable cell such as CD47. Interaction of CD47
with SIRPɑ on macrophages
negatively regulates phagocytosis
and prevents inappropriate
engulfment.

Resolution of
Inflammation
To prevent the inflammatory CALR
apoE
LRP1

consequences associated with Apoptotic cell PS

Gas6
MertK

the accumulation of apoptotic MFG-E8 TG2

debris, dying cells are efficiently avß3 integrin

cleared through a process known SR-B1

Macrophage
as efferocytosis. Efferocytosis
is mediated by macrophages TIM
detecting ‘eat me’ signals such as
phosphatidyl serine externalization
on the target cell, and can be
countermanded by cell surface
expression of anti-phagocytic ‘don’t
eat me’ signals such as CD47.

Stressed-but-viable neuron Neuronal

Reversible 'eat me'
signal exposure pruning
Phagoptosis is the killing and
removal of stressed but viable
neurons by microglia, the resident
macrophages of the brain. This is
Phagocytic
Execution of neuronal death recognition a key process in neuronal network
through phagocytic uptake development and maturation.
Dynamic regulation of CD47
signaling between stressed
neurons and microglia is a critical
determinant of neuronal pruning.

Tumor CD47

Survival
SIRPα

Tumor cells exploit ‘don’t eat

me’ signaling pathways to avoid Macrophage Tumor cell
engulfment by macrophages.
Expression of CD47 provides a ‘cloak’
for the tumor cell to evade detection 'Don't eat me'
by the host’s immune system.

CD47 Therapeutics: antibodies against CD47, TSP-1

derived peptides, small molecules

1 2

1. CD47 is a ‘don't eat me’ signal expressed by cells 2. Binding CD47 using an antibody, peptide or small
to avoid phagocytosis. It is highly expressed on molecule blocks the ‘don't eat me’ signal and can
the surface of  tumor cells and is recognized by allow tumor cells to be targeted by macrophages.
macrophages via the SIRPɑ ligand.

3. Once the macrophage has recognized the target 4. The membrane fully engulfs the target, forming a
cell, the cytoskeleton rearranges to engulf the target phagosome. This fuses with lysosomes in the cytosol
cell. Actin polymerizes and lipids polarize to enable to form acidic phagolysosomes where enzymes
the membrane to extend around its target. destroy the target cell.

3 4

The time course of events and morphological changes that occur in cell-cell interactions are complex
and dependent on many factors including experimental set up, concentration of inhibitors and specific
cell types. IncuCyte® real-time live-cell analysis is ideally suited to following and quantifying this
biology in vitro – the image-based, non-perturbing nature of the method provides uniquely dynamic
biological insight across the full time course at a throughput and ease that significantly enhances
research productivity. Using IncuCyte® detection probes and reagents, live-cell assays for CD47
modulators can be readily established to measure tumor cell proliferation, apoptosis, cell death and
macrophage engulfment.

CITATIONS
CD47 update: a multifaceted actor
in the tumour microenvironment
of potential therapeutic interest.
Martiny et al. British Journal of
Pharmacology (2012) 167 1415–1430.
CD47 is upregulated on
circulating hematopoietic stem
cells and leukemia cells to avoid
phagocytosis. Weissman et al. Cell
(2009) 138, 271–285.
Therapeutic opportunities for
targeting the ubiquitous cell surface
receptor CD47. Roberts et al. Expert
Opin Ther Targets (2013) 17(1),
89–103.
Microglial phagocytosis of live
neurons. Brown & Neher. Nature
Reviews Neuroscience (2014) 15,
209–216.

ADDITIONAL RESOURCES
Learn more about IncuCyte® real-time, automated phagocytosis assays
Webinar: Real-time analysis of cellular phagocytosis

essenbio.com