Pancreatic cancer puts up a strong defense against the immune system, preventing important cancer-fighting immune cells and immunotherapy treatments from reaching the tumor and doing their job. UNC Lineberger researchers are working on an innovative solution to this problem.

UNC Lineberger’s Paul Dayton, PhD, and Yuliya Pylayeva-Gupta, PhD, are studying whether they can use tiny, engineered microbubbles and ultrasound imaging to improve the activation of the immune system against pancreatic cancer, one of the deadliest cancers.

Backed by a seed grant from UNC Lineberger, the researchers are launching early laboratory studies into whether they can deliver microbubbles directly to tumor models.

Using microbubbles and ultrasound imaging to trigger an immune response

Using ultrasound imaging, they can non-invasively track the bubbles’ exact location within the body. Once the microbubbles reach the tumor, they want to use ultrasound waves to cause the bubbles to vibrate quickly and bump into the tumor cells.

Caption available.
UNC Lineberger’s Paul Dayton, PhD.

“When you have a bubble in the body, and it’s exposed to ultrasound, the bubble oscillates,” said Dayton, interim chair of the UNC/NC State Joint Department of Biomedical Engineering. “Think of it as a bell that you hit with a hammer. It rings. As it oscillates, it’s physically changing shape, in doing that, it’s mechanically agitating everything around it, including the tumor cells.”

Researchers want to study whether the vibration will cause pancreatic cancer cells to release molecules that trigger the immune system.

“We are studying whether the microbubbles will stimulate these cells to release signatures that trigger the immune system, or break the cells up so that the body can recognize them as non-natural, invasive particles,” Dayton said.

While forms of ultrasound can be used at high energy levels to kill cells, Dayton said researchers want to study the best way to stimulate the bubbles to trigger an immune response, since there are different ranges of ultrasound that can be used.

“Focused ultrasound treatment is already used clinically,” he said. “What we’re looking at is if we can use it in lower power ranges to see what creates the best immune response.”

Understanding pancreatic cancer

Yuliya Pylayeva-Gupta
UNC Lineberger’s Yuliya Pylayeva-Gupta, PhD.

Pancreatic cancer has multiple defenses against the immune system, said Pylayeva-Gupta, assistant professor in the UNC School of Medicine Department of Genetics. The project is just one effort she is leading to understand the immunosuppressive effects of these tumors and to find ways to trigger the immune system to be more active against this disease.

One of the issues is a lack of access to tumors by certain cells called antigen-presenting cells. Normally, these cells act as scouts, roaming the body to look for bacteria, viruses and infected cells. They present evidence of infected cells or tumors to immune cells called T-cells, which then seek and destroy based on the scouts’ instruction. She said microbubbles might help with this access problem.

“Based on other published work and our preliminary studies, what we think might be happening is several things: There is some degree of tumor cell death due to the microbubble activity that might increase the activity of antigen-presenting cells, and second, there might be an increase in vascular permeability, allowing the cells that are carrying the antigen to exit the tumor and reach the T-cells,” Pylayeva-Gupta said.

Beyond this study, these researchers are planning additional studies to investigate other ways of boosting the immune response to pancreatic cancer.