New findings from Cold Spring Harbor Laboratory (CSHL) shed new light on pancreatic cancer. Researchers found that pancreatic cancer triggers an immune response, contradicting previous ideas that pancreatic cancer suppresses immunity. Their study focused on pancreatic ductal adenocarcinoma (PDAC) and revealed consistent antibody responses across patients, which could provide new avenues for treatment development.
As a postdoc in the lab of CSHL Professor Douglas Fearon, Min Yao studied pancreatic cancer cells (pictured above in red) to better understand how they interact with the immune system. Phelan noted that this basic research would not be possible without the generous support of the Simons Foundation. Image credit: Fearon Laboratory/Cold Spring Harbor Laboratory
More than 90% of pancreatic cancer cases are attributed to an aggressive, fatal disease called pancreatic ductal adenocarcinoma (PDAC). Researchers know very little about how our immune system interacts with PDAC. So coming up with treatments can be tricky. It is thought that patients do not show a natural immune response to cancer because the tumor environment somehow prevents this response. Many people simply don't believe that PDAC interacts with the immune system.
CSHL scientists have now confirmed that pancreatic cancer does trigger a response from our immune system. However, T cells that help fight most diseases have difficulty infiltrating PDAC tumors. These findings may help guide future efforts to develop treatments.
In the study, CSHL Professor Douglas Fearon worked with a team that included lead author Min Yao, Professor Matthew Weiss of the Zucker School of Medicine, and CSHL Partners for the Future project participant Sophia Shen from Cold Spring Harbor High School. They first set out to find a neoantigen that was present only in PDAC tumors and not in normal tissue. The body produces cells called antibodies that recognize specific antigens and help destroy them. Identifying new PDAC antigens could help explain why some patients have better outcomes than others.
Unexpected discoveries and impacts
The research team sequenced plasma cells in pancreatic tumor samples from seven NorthwellHealth patients. They then created synthetic antibodies based on that sequence. The idea is that the synthetic antibodies will lead the team to search for new PDAC antigens behind the body's immune response. But they didn't find what they were looking for. Instead, they found 25 antibodies that responded to antigens produced by cancer cells and normal cells in the body, and these antibodies were consistent between patients.
"I was surprised by the clarity of the data, that we had many antibodies reacting to the same antigen from multiple patients," Phelan said.
Previously, researchers had thought pancreatic cancer suppressed immunity. Some are even exploring vaccination as a possible solution. Based on his team's findings, Phelan said this strategy may not be needed.
"Pancreatic cancer is not immunologically silent. That's the message," Phelan explained. "Pancreatic tumors are already immunogenic. We face the challenge of getting the immune response to attack the cancer."
Now that scientists understand the problem better, they can try to develop feasible solutions. This is real progress and a welcome development for the pancreatic cancer community.