Researchers find potential key to unlocking the immune system in pancreatic cancer

August 6, 2018 by Laura Oleniacz, University of North Carolina at Chapel Hill School of Medicine
Researchers find potential key to unlocking the immune system in pancreatic cancer
When IL35 is missing from preclinical models, cancer-killing immune cells (stained brown) can enter tumors.

A University of North Carolina Lineberger Comprehensive Cancer Center study may provide insights into how to overcome barriers to using immune-based treatments for pancreatic cancer, the third most deadly cancer in the United States.

In the journal Cancer Immunology Research, scientists revealed that a molecule called interleukin-35 plays a role in suppressing cancer-fighting immune in . They also reported that their preclinical study showed that knocking out IL35 worked well alongside drugs that unleash the immune system against cancer, helping to shrink tumors.

"Immunotherapies have been very effective at reducing the tumor burden in cancers such as melanoma, but this type of treatment hasn't worked right off the bat in cancer," said UNC Lineberger's Yuliya Pylayeva-Gupta, Ph.D., assistant professor in the UNC School of Medicine Department of Genetics. "That's because in pancreatic cancer, the immune cells that are present in the tumor are not the ones that respond to immunotherapy. We now better understand how these cells are suppressing the anti-tumor response."

Pancreatic cancer is one of the deadliest cancers in the United States, with just 8.5 percent of patients living five years following diagnosis. Pancreatic cancer is often diagnosed at late stages, which contributes to poor outcomes, and many cancers are not eligible for surgery because they spread to surrounding organs, or encapsulate vital blood vessels.

"We need some sort of agent that can shrink the tumors maybe to the point where we can take them out during surgery, or shrink them and obliterate them all together," she said.

Immune-based treatments known as checkpoint inhibitors have been effective in treating some cancers, including advanced melanoma. While scientists have discovered there are often within pancreatic cancer tumors, responses to immune-based treatments have been ineffective in , researchers report.

"The cells present are the ones that are what we call 'immunosuppressive cells,'" Pylayeva-Gupta said. "This cell type creates a barrier that does not allow T lymphocytes to come in."

Researchers evaluated what immunosuppressive cells are doing to create the barrier. They found cytokine IL35 suppresses the immune response that could fight the cancers. Laboratory models lacking IL35 had reduced growth, and they showed improved response by -killing cells. The researchers discovered a synergism when they added in checkpoint inhibitors to their models lacking IL35.

"We found that if we eliminated cytokine IL35 from the system, it would work to reduce ," she said. "Take away IL35, and you also see the increases in T cell lymphocytes. That's what you really want for immunotherapy."

Explore further: Study reveals secrets of "hot" and "cold" pancreatic cancer tumors

More information: Bhalchandra Mirlekar et al. IL-35 hinders endogenous anti-tumor T cell immunity and responsiveness to immunotherapy in pancreatic cancer, Cancer Immunology Research (2018). DOI: 10.1158/2326-6066.CIR-17-0710

Related Stories

Study reveals secrets of "hot" and "cold" pancreatic cancer tumors

June 28, 2018
So-called "hot" tumors filled with T cells are often considered to be more sensitive to immunotherapy compared to "cold" tumors with fewer T cells, but a clear demonstration of why has eluded cancer biologists—until now. ...

Gut bacteria determine speed of tumor growth in pancreatic cancer

March 22, 2018
The population of bacteria in the pancreas increases more than a thousand fold in patients with pancreatic cancer, and becomes dominated by species that prevent the immune system from attacking tumor cells.

Pancreatic tumors may require a one-two-three punch

January 15, 2018
One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a new Wilmot Cancer Institute study, scientists discovered ...

Immune system infighting explains pancreatic cancer's aggression

August 25, 2016
Internal conflict between cell types explains why the immune system struggles to recognize and attack pancreatic cancer. Curbing this infighting has the potential to make treatment more effective, according to a study led ...

Bladder cancer model could pave the way for better drug efficacy studies

May 21, 2018
Understanding that not all bladder cancers are the same, researchers at the University of North Carolina Lineberger Comprehensive Cancer Center have created a tool that may help them to uncover why only a fraction of patients ...

Study sheds light on why some breast cancers have limited response to immunotherapy

August 21, 2017
UNC Lineberger Comprehensive Cancer Center researchers have identified a possible reason why some aggressive breast cancers are unresponsive to certain immunotherapy treatments, as well as a potential solution.

Recommended for you

Healthy diets linked to better outcomes in colorectal cancer

October 20, 2018
Colorectal cancer patients who followed healthy diets had a lower risk of death from colorectal cancer and all causes, even those who improved their diets after being diagnosed, according to a new American Cancer Society ...

Scientists to improve cancer treatment effectiveness

October 19, 2018
Together with researchers from the University of Nantes and the University of Reims Champagne-Ardenne in France, experts from the National Research Nuclear University MEPhI have recently developed a quantum dot-based microarray ...

Why some cancers affect only young women

October 19, 2018
Among several forms of pancreatic cancer, one of them specifically affects women, often young. How is this possible, even though the pancreas is an organ with little exposure to sex hormones? This pancreatic cancer, known ...

Mutant cells colonize our tissues over our lifetime

October 18, 2018
By the time we reach middle age, more than half of the oesophagus in healthy people has been taken over by cells carrying mutations in cancer genes, scientists have uncovered. By studying normal oesophagus tissue, scientists ...

Study involving hundreds of patient samples may reveal new treatment options of leukemia

October 17, 2018
After more than five years and 672 patient samples, an OHSU research team has published the largest cancer dataset of its kind for a form of leukemia. The study, "Functional Genomic Landscape of Acute Myeloid Leukemia", published ...

A 150-year-old drug might improve radiation therapy for cancer

October 17, 2018
A drug first identified 150 years ago and used as a smooth-muscle relaxant might make tumors more sensitive to radiation therapy, according to a recent study led by researchers at The Ohio State University Comprehensive Cancer ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.