Curbing inflammation after radiation therapy slows pancreatic tumor growth in mice

cancer
Blocking inflammation following radiation therapy slowed pancreatic tumor growth and improved survival in mice.

Though relatively rare in the U.S., pancreatic cancer is one of the deadliest forms of the disease, with a five-year survival rate of 7%. University of Pennsylvania scientists have zeroed in on a resistance mechanism that plays a role in making it so difficult to treat: inflammation that occurs in response to treatment.

Pancreatic tumors’ resistance to treatment could come from a protective “tumor microenvironment,” the scientists said in a statement. That microenvironment comprises inflammatory white blood cells called monocytes and macrophages.

“We know that if you take these tumor cells out of a patient and put them in a petri dish, they can be killed by chemotherapy,” said Dr. Gregory Beatty, an assistant professor of hematology/oncology at Penn and principal investigator of the study. “But in the body, within the microenvironment they create, they somehow manage to resist elimination even by our most cytotoxic therapies.”

The Penn team discovered comparatively high levels of inflammatory compounds in mice with pancreatic tumors. These included CCL2, the signaling molecule that activates CCR2, a receptor on some white blood cells that promotes their recruitment by tumors. The mice’s CCL2 levels increased further after they received radiotherapy. The scientists found that the tumors themselves were secreting the molecule. Tumor growth in these mice slowed “modestly” compared to untreated mice.

But mice treated with chemo and a CCL2-blocking antibody showed dramatically slower tumor growth and their tumors’ recruitment of monocytes and macrophages was “sharply reduced,” the researchers reported. Mice who got the combination treatment survived roughly 25% longer than those who received radiation alone. The results were published in Clinical Cancer Research.

While the approach is promising, it “doesn’t cure the mice—there’s still more to be done,” Beatty said. The team plans to look into tumor-associated inflammatory cells and radiation therapy in human patients. They will also try to unravel why radiation therapy provokes an antitumor response in a patient’s T cells in other cancers but not in pancreatic cancer.

Other approaches to pancreatic cancer include altering tumor metabolism with CDK4/6 inhibitors and using an implantable device to deliver chemotherapy to hard-to-reach tumors.