Pancreatic cancer remains one of the deadliest forms of the disease, often diagnosed late and proving resistant to existing treatments. Now, a team at Northwestern Medicine has identified a critical reason why this cancer evades the immune system: tumors disguise themselves with a sugar-based coating, effectively hiding from immune cells. Researchers have developed an experimental antibody that removes this disguise, allowing the body’s own defenses to recognize and attack the cancer.
The Immune Evasion Mechanism
For years, scientists have struggled to understand why immunotherapies – treatments designed to harness the immune system – fail so often in pancreatic cancer. This new research reveals that tumors exploit a natural defense mechanism used by healthy cells. Healthy cells display a sugar called sialic acid, signaling the immune system not to attack. Pancreatic cancer cells mimic this signal, coating themselves in the same sugar and tricking immune cells into ignoring them.
“In short, the tumor sugar-coats itself – a classic wolf-in-sheep’s-clothing move – to escape immune surveillance,” explains study senior author Mohamed Abdel-Mohsen.
This sugar-coated disguise binds to a receptor on immune cells, called Siglec-10, which sends a “stand down” signal, preventing an immune response. The team identified this mechanism after six years of work, demonstrating that blocking it with a monoclonal antibody can restore immune activity.
Antibody Restores Immune Function in Mice
Preclinical studies in mice showed that the experimental antibody successfully blocked the sugar-based deception. Immune cells, once suppressed, began attacking cancer cells, slowing tumor growth significantly. The process required extensive testing: thousands of antibody candidates were screened before identifying one that effectively neutralized the tumor’s disguise.
“Seeing it work was a major breakthrough,” says Abdel-Mohsen.
Preparing for Human Trials
The researchers are now refining the antibody for use in humans, preparing for early-stage safety and dosing studies. They are also exploring how it can be combined with chemotherapy and other immunotherapies to achieve more aggressive results.
“There’s a strong scientific rationale to believe combination therapy will allow us to reach our ultimate goal: a full remission,” Abdel-Mohsen states. “We don’t want only a 40% tumor reduction or slowing down. We want to remove the cancer altogether.”
In addition to clinical trials, the team is developing a diagnostic test to identify patients whose tumors rely on this sugar-based evasion strategy, enabling more targeted treatment. If progress continues as expected, the treatment could be available to patients within five years.
Broader Implications for Cancer and Immunology
This breakthrough extends beyond pancreatic cancer. Researchers are investigating whether the same sugar-coating trick is used by other difficult-to-treat cancers, such as glioblastoma, and whether it plays a role in non-cancerous diseases where immune deception occurs. The study contributes to the growing field of glyco-immunology, which explores how sugars influence immune responses.
The implications of these findings may eventually expand beyond cancer treatment, potentially leading to new therapies for infectious diseases and age-related conditions.
This research represents a significant step forward in understanding and combating pancreatic cancer, offering a new approach to awaken the immune system against one of the most lethal forms of the disease.
