and Evades Treatment
Researchers have developed a new computational tool, FunCN (Functional Cellular Neighborhoods), to better understand how pancreatic cancer spreads and resists treatment. Unlike older methods that look at only nearby cells, FunCN measures how all surrounding cells influence each other, giving a more detailed map of the tumor microenvironment.
Using FunCN, the team analyzed over 267,000 cells from primary pancreatic tumors and liver metastases. They found that immune cell patterns differ by location: primary tumors are rich in certain myeloid cells and fibroblasts, while liver metastases have more regulatory T cells, neutrophils, and antigen-presenting fibroblasts. They also discovered that CD8+ T cells, which fight tumors, show signs of exhaustion depending on their neighborhood, with different immune “brakes” active in the pancreas versus the liver. In the liver, neutrophils interact with the immunosuppressive molecule VISTA, helping tumors evade therapy.
The study highlights that metastatic pancreatic cancer adapts differently at each site, suggesting that treatments need to be tailored. Targeting neutrophils or VISTA in liver metastases, for example, may help restore immune attack. Overall, the findings point toward personalized, site-specific strategies to improve outcomes in this aggressive cancer.