UAB Comprehensive Cancer Center Magazine Spring 2017 | Page 6
and Cancer Center senior scientist. Much of this work is
find ways to control that degree of exhaustion and/or extend
conducted through the center’s Inflammation, Immunology
the time that activation is maintained, which would allow
and Immunotherapeutics Research Program, which Dr.
for a better immune response.
Buchsbaum co-leads with senior scientist Troy Randall,
The BCRFA has also awarded a grant to Dr.
Ph.D.
Buchsbaum and Sara Cooper, Ph.D., with the
One such project involves patients with triple negative
HudsonAlpha Institute for Biotechnology in Huntsville,
breast cancer, a particularly aggressive and difficult-to-treat
to investigate what is referred to as the immune repertoire,
form of the disease. An earlier clinical trial conducted at the
the number of different sub-types of T cells made by the
Cancer Center and led by senior scientist Andres Forero,
immune system. In this study, the Cancer Center provides
M.D., and Cancer Center director emeritus Albert LoBuglio,
HudsonAlpha tumor samples, and through genomic testing,
M.D., examined triple negative breast cancer patients who
they identify the number of T cell clones within that tumor.
responded to therapy versus those who did not. Through
Researchers at HudsonAlpha have shown that in animal
genomic analysis of tumor specimens, they discovered that
models, after transfecting (or inserting) a transcription
patients who responded to treatment expressed MHC II
factor into the tumor model, there was no difference in the
genes, which are associated with immune activation, and
distribution of T cell clones in the animal that was immune
the non-response patients did not.
responsive to the tumor versus not.
With funding support from the
Researchers did see, however, a
“The
concept
of
using
Breast Cancer Research Foundation
large increase in the size of the T cell
immunotherapy dates as
of Alabama (BCRFA), that work
clones within the responsive tumor
has been and continues to be studied
compared to the non-responsive. The
far back as the late 1800s.
in animal models to develop new
significance of this finding is that
It’s
incredibly
exciting
that
a
techniques for future clinical trials.
it potentially allows for monitoring
century-plus later we have
“In certain breast cancer animal
immune activation in a real-time
models, we have found that the use of
basis.
real evidence that we can
HDAC inhibitor can upregulate the
“If these activated T cells are
put
into
practice.”
transcription factors associated with
present in one patient and not
the MHC II pathway,” Dr. Buchsbaum
another, then you know to continue
Donald
Buchsbaum,
Ph.D.,
says. “Our intent is to study that in
to treat the patient whose immune
professor and direc tor of the UAB
combination with checkpoint inhibitor
system is being activated and try a
Division of Radiation Biology and
antibody therapy and to use other
different approach in the other,” Dr.
Cancer Center senior scientist
procedures to further enhance that
Buchsbaum says. “There is no benefit
response.”
from a patient not responding and just
At the same time, the Cancer Center is also involved in
waiting to see if they do. If we can measure the size of the
a clinical trial examining HDAC inhibitor in combination
clones of active T cells, then we have a way to monitor the
with checkpoint inhibitor antibody therapy for triple
activation of the T cells. Currently, we don’t know how to
negative breast cancer patients. “We’re studying in parallel
gauge the level of response. We need real-time monitoring,
in the laboratory as well as clinical trials this approach
and this approach allows us to do that.”
to enhancement of immune activation and response,” Dr.
Immunotherapy research also plays a role in
Buchsbaum says. This work is a collaboration among him,
understanding cancer metastasis, says Lalita Shevde-
Drs. Randall and Forero, as well as Mei Li, Ph.D., and
Samant, Ph.D., professor in the UAB Department of
M.D.-Ph.D. student Tyler McCaw.
Pathology and Cancer Center senior scientist (see Scientist
Another promising project, which is being led by
Profile, page 21). Dr. Samant is currently investigating
Dr. Randall, is examining the phenomenon of T cell
the cross-talk between breast cancer cells and cells of the
exhaustion. Studies in some animal models have shown that
innate immune system known as macrophages. Cancer cells
when MHC II expression is increased, there is a period of
tend to reprogram and polarize these macrophages and
tumor regression, followed by tumor regrowth – meaning
make them allies by fostering tumor growth. Dr. Samant’s
that the activated immune cells are becoming exhausted and
laboratory is investigating how morphogens from the
no longer effective. Dr. Randall and his team are trying to
hedgehog signaling pathway communicate from the breast
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