Jefferson Scientists Find Protein Helps Pancreatic Cancer Cells Hide from Immune System, Allowing Spread
A protein that helps prevent a woman’s body from rejecting a fetus may also play an important role in enabling pancreatic
cancer cells to evade detection by the immune system, allowing them to spread in the body.
Researchers
at Jefferson’s Kimmel Cancer Center in Philadelphia found that the
metastatic cancer cells in the lymph nodes of patients with pancreatic
cancer produce enough of the protein, IDO, to essentially wall-off the
immune system’s T-cells and recruit cells that suppress the immune
system’s response to the tumor. The findings might mean not only a
better way to detect pancreatic cancer spreading to lymph nodes, but
also could enhance tumor immune therapy strategies against the
fast-moving, deadly disease.
According
to Jonathan Brody, Ph.D., assistant professor of Surgery at Jefferson
Medical College of Thomas Jefferson University, one way that metastatic
cancer cells can survive in nearby lymph nodes is by avoiding the
immune system. Evidence from studies by scientists looking at other
cancers has indicated that IDO (indolamine 2’3 dioxygenase) is critical
to regulating the “immune environment.” The Jefferson scientists wanted
to know if metastatic pancreatic cancer cells residing in the lymph
nodes expressed IDO to avoid being found, and if so, could they target
this enzyme with available drugs to prevent the cancer cells from
hiding from the immune system.
Dr.
Brody, Charles Yeo, M.D., Samuel D. Gross Professor and chair of
Surgery at Jefferson Medical College and their co-workers analyzed IDO
expression in 14 lymph nodes to which pancreatic cancer cells had
spread and compared them to the primary tumors that had not spread in
the same patients. In every case, they found greater expression of the
IDO protein in the cancerous lymph nodes. They also looked at three
cases of lymph node-negative pancreatic cancers, finding little IDO
present.
Scientists
know that IDO shuts off tryptophan production in T-cells, putting them
in a resting state, and recruits a different type of immune cell called
T-regulatory cells, which can inhibit the immune system. “If cells are
escaping the primary tumor and going into another environment such as
the lymph nodes, what are they doing to evade detection by the immune
system?” says Dr. Brody. “These data point to the fact that IDO may
play a role in helping cancer cells avoid the immune system.” His team
reported its findings at the recent meeting of the Southern Surgical
Association in Hot Springs, VA. The results have been accepted for
publication in the Journal of the American College of Surgeons.
The
group also examined pancreatic cancer cell lines in the laboratory for
IDO expression. Using antibodies to IDO, they didn’t find any IDO
expression until they treated the cells with interferon to mimic the
conditions in the lymph nodes. The tumor cells were then able to make
the enzyme.
Whether
or not the cancer has spread to the lymph nodes can affect a patient’s
prognosis, particularly after surgery. While scientists know a great
deal about how a pancreatic cancer develops from a pre-cancerous growth
into a cancer, they still don’t have a clear understanding of how it
progresses from a primary cancer to metastatic disease. IDO, Dr. Brody
says, may play an important part in the process.
“The
immune system appears to have a balance that can allow cancer cells to
grow but also can detect and destroy them, Brody explains. “While IDO
is crucial toregulating this balance, too much IDO tips the balance
toward an immune suppression, supporting cancer growth.”
Dr.
Brody notes that IDO inhibitors are available clinically, and these
could in theory be used with chemotherapy or perhaps other forms of
immune therapy against pancreatic cancer. An inhibitor might be able to
activate T-cells to kill cancer cells, for example. “Presumably we
could give IDO inhibitors up front to patients who we know are lymph
node-positive to try to reduce the cancer and possibly convert them to
surgical candidates,” he explains.
Pancreatic
cancer, the fourth-leading cause of cancer death in this country, takes
some 33,000 lives a year. The disease is difficult to treat,
particularly because it is frequently detected after it has spread to
other areas on the body. Only 5 percent of all individuals with
pancreatic cancer live for five years after diagnosis, and
approximately 25 percent of those diagnosed with pancreatic cancer who
undergo successful surgical removal of their disease live at least that
long. But recent figures give new hope: of those who live for five
years after surgical resection, some 55 percent will be alive at least
another five years.
Media Only Contact:
Steve Benowitz
Thomas Jefferson University Hospital
Phone: (215) 955-6300
Published: 1/10/2008