Delphine J. Lee, MD, investigator at The Lundquist Institute for Biomedical Innovation, and a team of researchers identified a new immunotherapy strategy that may help overcome one of the greatest challenges in treating pancreatic cancer: the tumor’s ability to suppress the body’s immune response. The findings, published in the Journal of Gastroenterology, provide important insights into how activating the immune system could slow disease progression and improve outcomes for patients with pancreatic ductal adenocarcinoma (PDAC).
PDAC is the most common form of pancreatic cancer and remains one of the deadliest cancers worldwide. Despite advances in surgery and chemotherapy, survival rates have improved only modestly over the past several decades. A major reason is that pancreatic tumors create a hostile environment that prevents immune cells from effectively recognizing and attacking cancer cells, limiting the success of existing immunotherapies.
In this study, researchers focused on a molecule known as GITR, which plays a key role in regulating immune cell activity. By activating GITR, the team aimed to shift the tumor environment from one that suppresses immune responses to one that supports them.
Using a preclinical model of pancreatic cancer, the researchers found that activating GITR significantly slowed tumor growth and extended survival. The treatment reduced the presence of immune cells that normally dampen immune responses and increased the activity of cancer-fighting immune cells.
“Pancreatic cancer has challenged us for a long time, especially because it tends to be what we call ‘immunologically cold,’ meaning it doesn’t respond well to many immunotherapies. But discoveries like the GITR pathway give me real hope. We’ve seen how powerful the immune system can be in other cancers—sometimes even clearing the disease entirely. Our goal is to help unlock that same potential for patients with pancreatic cancer,” said Dr. Lee.
To assess the relevance of these findings for patients, the team also analyzed pancreatic cancer tissue from individuals undergoing treatment. They observed higher levels of GITR in tumor tissue compared to healthy pancreatic tissue, particularly in patients who had received chemotherapy prior to surgery. This suggests that standard treatments may help prepare tumors to respond to GITR-based immunotherapy.
Notably, patients whose tumors contained higher numbers of GITR-positive immune cells tended to experience better long-term outcomes. This finding highlights the potential of GITR not only as a therapeutic target, but also as a biomarker to help identify patients who may benefit most from immune-based treatment strategies.
While additional research is needed, the findings lay important groundwork for future therapies that integrate immunotherapy with chemotherapy or other standard treatments—an approach that could represent a meaningful step forward for patients facing a cancer with limited treatment options.