Immune therapy has not worked well in pancreatic cancer because of the cancer’s inherent immune resistance. Scientists at Sylvester have discovered a way to outsmart the deadly cancer’s ability to prevent immune checkpoint inhibitor therapy from killing pancreatic cancer cells. 

The Sylvester research team targeted a long-ignored pancreatic cancer metabolic pathway, called the hexosamine biosynthesis. Their results were  published October 15, 2019 in the Journal of Clinical Investigation. 

“Pancreatic tumors are notoriously immune resistant, partly because there is a lot of heterogeneity within the tumor but mostly because of the dense stroma that acts as a barrier preventing cytotoxic immune cells to infiltrate the tumor and eradicate the cells,” said study author Sulagna Banerjee, Ph.D., associate professor of surgery.

Dr. Banerjee and colleagues found that targeting glutamine in the hexosamine biosynthesis metabolic pathway in pancreatic cancer weakens the wall-like stroma and allows immune cells to infiltrate. The tumor then becomes susceptible to immune therapy. 

“The key finding is that by inhibiting this metabolic pathway inside the tumor cells, we were able to program the tumor microenvironment to let in cytotoxic immune cells. The inhibitor also inhibits cancer stem cells,” Dr. Banerjee said. “To the best of my knowledge, this is the first time anyone has shown sensitization to immune therapy using a metabolic inhibitor in pancreatic cancer,” said Dr. Banerjee.