Main roads
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New research helps explain why pancreatic cancer doesn’t respond to existing cancer drugs
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Experimental immunotherapy tests in mice are encouraging
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The treatment turns the immune cells into tumor cell killers
SUNDAY, April 19, 2026 (NewsDay News) – Immunotherapy has largely failed as a treatment for pancreatic cancer, and researchers have missed a key reason.
Pancreatic tumors reprogram immune cells that normally turn off tumor-killing cells, according to a team at Oregon Health University in Portland.
“Pancreatic cancer is extremely resistant to most treatments,” said the senior author Kathleen Byrneassistant professor, OHSU School of Medicine.
“Even when we know that the immune system is capable of long-term protection, it has been very difficult to get this response to work in this disease,” he said in a news release.
Immunotherapy like immune checkpoint inhibitors revolutionized the treatment of melanoma and lung cancer. But they did not show the same benefit for pancreatic cancer, the third leading cause of cancer-related death in the US.
The presence of pancreatic tumors with a large number of regulatory T cells (Tregs) is the main cause. Simply put, they inhibit the immune cells that are capable of killing tumors.
“If there are a lot of them in a tumor, it’s very difficult to get an anti-tumor immune response,” Byrne said.
He and his team report in this month’s journal Immunity in experimental immunotherapy mouse trials.
Known as a CD40 agonist, it differs from standard checkpoint inhibitors.
Rather than targeting a single immune signal, it activates a broader response.
And it not only activated tumor-killing cells, the researchers were surprised to find, but also transformed them into cells that supported anti-tumor activity.
“We didn’t expect that,” Byrne said. “The cells that were shutting down the immune response suddenly started killing the tumors.”
The findings explain why many immunotherapies don’t work in pancreatic cancer and suggest a possible solution.
Treatments can attack with a double whammy – activating the immune system while overcoming the tumor’s own ability to turn it off.
The researchers said that while the results of animal studies often differ from those in humans, the discovery could be useful in treating a disease in which most patients stop responding to available treatments.
Combo strategies can make immunotherapy useful, Byrne said.
The research also points to the possibilities of combining immune-based therapies with newer cancer drugs, such as KRAS inhibitors, which directly attack pancreatic cancer cells but still rely on immune support.
“You can imagine hitting cancer cells with a targeted drug and reprogramming the immune environment around it,” Byrne said. “This combination may be more effective than either approach alone.”
Clinical trials using this combo therapy should be conducted in humans within the next few years, he said.
Her lab is now working to better understand the communication between immune cells within pancreatic tumors and to determine if the reprogrammed cells offer long-term protection.
More information
There is more information about pancreatic cancer Pancreatic Cancer Action Network.
Source: Oregon Health & Science University, news release, April 10, 2026
What does this mean for you?
Researchers are working to develop effective treatments for pancreatic cancer.
