Northwestern Antibody Exposes Hidden Pancreatic Cancer Cells
- Pancreatic cancer is notoriously hard to treat and often resists the most advanced immunotherapies.
- For the first time, the team identified how this sugar trick works and showed that blocking it with a monoclonal antibody reawakens immune cells to attack cancer cells...
- "It took our team about six years to uncover this novel mechanism, develop the right antibodies and test them," said study senior author Mohamed Abdel-Mohsen, associate professor of medicine...
Pancreatic cancer is notoriously hard to treat and often resists the most advanced immunotherapies. Northwestern Medicine scientists have uncovered a novel explanation for that resistance: Pancreatic tumors use a sugar-based disguise to hide from the immune system. The scientists also created an antibody therapy that blocks the sugar-mediated “don’t-attack” signal.
For the first time, the team identified how this sugar trick works and showed that blocking it with a monoclonal antibody reawakens immune cells to attack cancer cells in preclinical mouse models.
“It took our team about six years to uncover this novel mechanism, develop the right antibodies and test them,” said study senior author Mohamed Abdel-Mohsen, associate professor of medicine in the division of infectious diseases at Northwestern University feinberg School of medicine.
“Seeing it work was a major breakthrough.”
The study will publish on Monday,nov. 3 in the journal cancer Research (published by the American Association for Cancer Research) to mark the start of Pancreatic Cancer Awareness Month.
Turning the immune system back on
Pancreatic cancer is among the deadliest cancers. It is often diagnosed late, with few treatment options and a five-year survival rate of just 13%. It also tends to resist immunotherapies that work well against other cancers.
Inside pancreatic tumors, the immune system response is unusually suppressed. “We set out to learn why, and whether we could flip that surroundings, so immune cells attack tumor cells instead of ignoring or even helping them,” Abdel-Mohsen said.
The team found that pancreatic tumors hijack a natural safety system used by healthy cells. In normal conditions, healthy cells express a sugar called sialic acid on their surface to signal to the immune system, “don’t harm me.”
The scientists found that pancreatic tumors exploit that system by loading the same kind of sugar onto a surface protein called integrin α3β1.That sugar coat allows the protein to bind to a sensor on immune cells called Siglec-10,sending a false “stand down” signal.
In short, the tumor sugar-coats itself – a classic wolf-in-sheep’s-clothing move – to escape immune surveillance.
Mohamed Abdel-Mohsen, associate professor of medicine, division of infectious diseases, Northwestern University Feinberg School of Medicine
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* What: pancreatic cancer tumors use a sugar disguise to evade the immune system.
* Where: Northwestern Medicine research.* When: Study published Nov. 3, 2023.