ASCB 2013 PressBook - page 9

T H E A M E R I C A N S O C I E T Y F O R C E L L B I O L O G Y
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10
News from
The American Society
for Cell Biology
53rd Annual Meeting
New Orleans, LA
December 14–18, 2013
Changing targets shakes
a deadly brain tumor
EMBARGOED
FOR RELEASE
10:00 am, U.S. Central Time
Tuesday, December 17, 2013
Contact
Johanna Joyce
Memorial Sloan-Kettering
Cancer Center
1275 York Avenue
New York, NY 10065
(646) 888-2048
Author presents
Tuesday, December 17, 2013
Presenting 3:50 PM–4:10 PM
Thread: Medicine
Minisymposium 18
Tumor Microenvironment as a
Driver and Target in Cancer
Progression
Presentation 207
Room 356
CSF-1R inhibition alters
macrophage polarization and
blocks glioma progression
J. Joyce
Cancer Biology and Genetics,
Memorial Sloan-Kettering Cancer
Center, New York, New York
This image shows part of a glioblastoma tumor from a mouse treated with
a CSF-1R inhibitor. The drug was shown to induce tumor-associated macro-
phages (green) to phagocytose or eat tumor cells (red).
Altering the tumor
microenvironment,
not the tumor,
yields startling
results by blocking
tumor-associated
macrophages in
glioblastoma
G
lioblastoma mul-
tiforme (GBM) is
the most common
and the most deadly adult
primary brain tumor, with
an average survival of just
14 months following diag-
nosis. Even with aggres-
sive treatment by surgery,
radiation, and chemotherapy, most thera-
peutic approaches targeting the glioma cells
in GBM fail. Faced with this bleak picture,
Johanna Joyce and colleagues at Memorial
Sloan-Kettering Cancer Center (MSKCC)
in NewYork City looked for an alternative
strategy and turned to non-tumor cells that
are part of the glioma microenvironment,
the cancer’s cellular neighbors. In particular,
they zeroed in on tumor-associated macro-
phages and microglia (TAMs). The results
were startling.
TAMs are resident macrophages, which
are normally the brain’s front-line immune
cells, and depend on colony-stimulating fac-
tor-1 (CSF-1) for differentiation and survival.
When the Joyce lab used an inhibitor of the
CSF-1 receptor (CSF-1R) to target TAMs in a
mouse model of GBM, the researchers saw
dramatic changes. The treated mice survived
many months beyond the control cohort.
Their established, high-grade gliomas re-
gressed in proliferation and malignancy,
even though the glioma cells themselves
were not the targets of the TAM treatment.
With the TAMs blockaded by CSF-1 inhibi-
tors, it was the tumor cells that showed in-
creased rates of apoptosis (programmed cell
death). The TAMs were not even depleted
in the treated mice, despite the drug block-
ade of their growth factor. Instead the TAMs
survived by responding to growth factors
secreted by the gliomas, including GM-CSF
and IFN-
γ
, according to Joyce.
Going one step further, the researchers
found that tumor spheres, freshly isolated
from glioma patients in the surgery depart-
ment at MSKCC, responded to the drug
when implanted in animals. The CSF-1R
blockade slowed intracranial growth in the
patient-derived glioma xenografts.
As the most common glioma, the GBM
genome was the first to be sequenced for
the Cancer Genome Atlas, which parsed
GBM into four genetic subtypes: proneural,
neural, classical, and mesenchymal. The
mice used in the Joyce lab experiments
model the proneural GBM subtype. All
forms of GBM have a 2- to 3-person per
100,000 incidence rate in the United States
and Europe, according to the National
Brain Tumor Society. Because of its highly
invasive phenotype, GBM is almost impos-
sible to resect completely in surgery. Drug
and radiation treatments are the standard
followups.
Joyce says that these new results, which
were first reported only two months ago in
Nature Medicine,
,
are encouraging for
planned clinical trials in glioma patients,
testing CSF-1R inhibitors in combination
with radiation therapy. “We are optimistic
that CSF-1R inhibitors may provide a more
effective therapy than current treatments
for the disease management of glioma
patients,” Joyce says.
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