Video by Rachel Hernandez, LJI Communications and Media Relations Coordinator
Your immune system is your best weapon against disease. Your immune cells jump into action any time a virus or bacterium tries to make you sick.
You even have specialized immune cells that scan your body for dangerous mutations. Each day, your immune system detects mutated cells and destroys them before they can grow into cancerous tumors.
If the immune system is so good at spotting danger, why do some tumors end up growing out of control?
Here’s what we know: Some tumors are “hot.” These tumors are made up of highly mutated cancer cells that just look wrong. The cells are teeming with dysfunctional proteins, they don’t mature properly, and they grow way too quickly. Your immune system sees these mutations and understands that these cells are a threat. The battle begins.
“Some tumors, like colon carcinoma, are very hot tumors. They have plenty of mutations, and that makes them more easily recognized by the immune system,” says LJI Instructor Remi Marrocco, Ph.D.
“Hot” tumors aren’t always easy to treat—some tumors grow too quickly—but they do attract more immune cell attention.
In recent years, scientists have developed life-saving cancer immunotherapies that help fight hot tumors. These immunotherapies direct the immune system’s T cells to seek out and destroy highly mutated cancer cells.
It’s much harder to fight “cold” tumors. Cold tumors contain relatively few mutations. These tumors blend into your organs and evade immune cell defenses—until it is too late. And because cold tumors don’t attract immune cell attention, they don’t usually respond to cancer immunotherapies.
“These tumors have the ability to function in stealth mode, where the immune system can no longer see them,” says LJI Associate Professor Chris A. Benedict, Ph.D.
Many cancers of the pancreas, breast, ovaries, and brain (glioblastoma) are cold tumors. Unfortunately, cold tumors often have low five-year survival rates. Pancreatic cancer has the lowest five-year survival rate at around 13 percent, according to the National Cancer Institute. “There is a desperate need for more therapies for pancreatic cancer,” says Marrocco.
Scientists today are investigating ways to heat up cold tumors. One promising strategy comes from a team of scientists at La Jolla Institute for Immunology (LJI) and UC San Diego, who are using viral molecules in a clever way.
A virus moves in
This new cancer treatment approach relies on a virus called cytomegalovirus (CMV). More than half of Americans are infected with CMV, and we don’t even know it. This species of herpesvirus rarely causes any symptoms. Instead, the immune system churns out virus-fighting T cells, and CMV retreats.
Benedict has dedicated much of his career to the science of CMV. He points out that CMV has a massive genome with more than 200 genes. For contrast, Ebola virus has just seven genes. “CMV has the largest genome of all the known viruses, and the virus dedicates nearly 50 percent of its genes to escaping our antiviral defenses,” says Benedict.
This means that even when our immune system steps up to fight CMV, the virus never truly leaves the body. Instead, CMV goes into dormancy, staying inactive and hidden, until — maybe — the immune system weakens and allows CMV to reactivate (for example, following immunosuppressive drugs in organ-transplant recipients). CMV’s presence in the shadows prompts the body to ramp up its population of CMV-fighting T cells.
Benedict’s lab studies these microscopic battles, fascinated by how the same molecules that our T cells use to fight CMV can also function to disrupt homeostasis of our immune systems and potentially trigger autoimmune disease during the virus’s lifelong latency-phase. As Benedict points out, many studies have highlighted the virus’s contributions to vascular disease.
“CMV shapes our immune systems to an enormous degree, even if we are healthy,” says Benedict.
Putting T cells to work against tumors
The LJI and UC San Diego scientists (led by Benedict and Tatiana Hurtado de Mendoza, Ph.D., Assistant Professor of Surgery at the UC San Diego School of Medicine) wanted to harness those T cells to go after pancreatic tumors.
“We’re taking T cells that are trained and really efficient at fighting that virus and redirecting them to kill the tumor instead,” says Marrocco.
To do this, the researchers injected mice carrying pancreatic tumors with peptides (small pieces of proteins) from CMV. The viral peptides worked as red flags to alert the immune system to danger. Suddenly, mouse T cells saw those “cold” pancreatic tumors as major threats.
This new experimental approach led to decreased tumor growth and longer survival in a mouse model of pancreatic cancer, according to a new report in the Journal for ImmunoTherapy in Cancer.
The researchers are now studying whether this approach also works against “cold” breast cancer tumors. No matter the cancer type, there’s hope we might bring the heat.
More cancer discoveries:
Now immune cells can see pancreatic tumors—and attack them
T cells can sense testosterone—What does that mean for prostate cancer therapies?
