Colon cancer is the second-leading cause of cancer-related death in
the United States, and despite advances in treatment, long-term survival of
patients with liver metastasis is rare.
A chemical found in tumors may help stop tumor growth, revealed a new study. Researchers at the University of Illinois at Chicago report that
increasing expression of a chemical cytokine called LIGHT in mice with
colon cancer activated the immune system's natural cancer-killing
T-cells and caused primary tumors and metastatic tumors in the liver to
‘Tumors exposed to LIGHT demonstrated an influx of T-cells that resulted in rapid and sustained tumor regression, even after expression of the cytokine stopped.’
LIGHT is an immune-stimulating chemical messenger previously found
to have low levels of expression in patients with colon cancer
The results are published in Cancer Research
"For most patients with colon cancer that has spread to the liver,
current treatments are palliative and not curative," says Dr. Ajay
Maker, associate professor of surgery in the UIC College of Medicine and
corresponding author on the paper. "And while studies have suggested
that immunotherapy may be a promising approach for advanced cancers, the
use of such treatments for advanced gastrointestinal metastases have
not yet been very successful."
Maker, a surgical oncologist, says that this study is exciting
because it looks at an immunotherapy intervention for a previously
unresponsive gastrointestinal cancer. The intervention, he says,
essentially trains the immune system to recognize and attack the tumor,
and to protect against additional tumor formation - a significant issue
in colon cancer.
Maker and his colleagues established colon cancer tumors in a mouse
model, in which the animals had an intact and unedited immune system.
Once tumors were sizable, the mice were randomized into two groups - one
group had the cytokine LIGHT turned on in the tumors, and the other
served as a control group for comparison.
Tumors exposed to LIGHT showed an influx of T-cells that resulted in
rapid and sustained diminishment in size, even after expression of the
cytokine stopped. In mice with liver metastases, expression of LIGHT
similarly provoked a potent immune response that resulted in a
significant decrease in tumor burden.
"We demonstrated that delivery of a therapeutic immune-stimulating
cytokine caused T-cells to traffic to tumors and to become activated
tumor-killing cells," Maker said. "This activity is especially exciting
because it resulted in a profound anti-tumor immune response without any
other chemotherapy or intervention. The treatment manipulates our
natural defenses to fight off the tumor in the same way it has been
trained to attack other foreign invaders in our body."
"Not only did we find that LIGHT expression promoted tumor
regression, upon further study we also identified the specific type of
T-cell - CD8 - that was responsible for shrinking the tumor," Maker
said. "These findings are powerful and have great clinical potential."