Immuno-Oncology Advances in Applied Cellular Analysis - 15

Advances in Applied Cellular Analysis * Blocking the "Don't Eat Me" Signal on Cancer Cells Lets Phagocytes Clean Up

antibody therapy was withdrawn. When the
antibody was administered to animals with already
evident tumors, further growth of the cancer was
halted, and metastasis prevented.
Importantly, the investigators also found that
human patients whose tumors expressed higher
levels of CD47 had poorer survival. Irving L. Weissman, M.D., and colleagues reported their findings
in PNAS, in a paper titled "The CD47-signal
regulatory protein alpha (SIRPα) interaction is a
therapeutic target for human solid tumors."

themselves against phagocytosis. For example,
the investigators cited evidence that CD47
expression is required to protect transfused red
blood cells, platelets, and lymphocytes from
rapid elimination by splenic macrophages. The
investigators also pointed out that CD47 is a
transmembrane protein that acts as a ligand
for signal regulatory protein-α (SIRPα), which is
expressed on macrophages and dendritic cells.
Binding of CD47 to SIRPα triggers a signaling
cascade that stops the CD47-expressing cells
from being phagocytosed.

The investigators reviewed evidence indicating
that cell surface expression of CD47 represents
a common mechanism by which cells protect

The study presented in the PNAS article was
designed to relate these observations more
specifically to tumor survival: "In vitro, blockade of

Administration of anti-CD47 antibodies inhibited tumor growth
in orthotopic immunodeficient mouse xenotransplantation
models established with patient tumor cells and increased
the survival of the mice over time."
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CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected," the article's authors wrote. "Administration of anti-CD47
antibodies inhibited tumor growth in orthotopic
immunodeficient mouse xenotransplantation
models established with patient tumor cells and
increased the survival of the mice over time."
The following year, the Stanford team went even
further, presenting evidence that macrophages
activated by the antibody therapy not only
engulf cancer cells, they also present pieces of
the cancer cells to CD8+ T cells, which, in addition
to attacking cancer, are also potent attackers of
virally infected or damaged cells. As a result, the
CD8+ T cells are activated to attack the cancer
cells on their own.
These results appeared in the PNAS in a
paper titled "Anti-CD47 antibody-mediated
phagocytosis of cancer by macrophages primes
an effective antitumor T-cell response." The
paper's lead author, M.D./Ph.D. student Diane
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Immuno-Oncology Advances in Applied Cellular Analysis

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