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The National Cancer Institute has awarded a five-year grant of more than $2.2 million to UNC Lineberger’s Yuliya Pylayeva-Gupta, PhD, to support her research into the immune response in pancreatic cancer, one of the deadliest cancers.

“Understanding the role of immune regulation in pancreatic cancer represents a crucial stepping stone on our way to advancing care for these patients,” said Pylayeva-Gupta, assistant professor in the UNC School of Medicine Department of Genetics. “In addition to furthering our basic understanding of tumor immunobiology, we hope this research will help guide the field toward the design of B-cell targeted therapies against pancreatic cancer.”

Pancreatic cancer has proven to be extremely difficult to treat, with just 9.3 percent of patients living five years following diagnosis. Immune-based treatments known as checkpoint inhibitors have been effective in treating some cancers. While scientists have discovered there are immune cells often within pancreatic cancer tumors, responses to immune-based treatments have been ineffective in pancreatic ductal adenocarcinoma.

“While recent successes of cancer immunotherapy have generated considerable excitement, this form of treatment has largely been ineffective in patients with pancreatic cancer,” Pylayeva-Gupta said. “A major barrier for immunotherapeutic approaches is immune suppression instigated by pancreatic tumor and stromal cells.”

Previously, Pylayeva-Gupta’s laboratory discovered that interleukin-35 plays a role in suppressing cancer-fighting immune cells in pancreatic cancer. This molecule – called a cytokine – is produced by B-cells, a type of immune cells that is responsible for creating disease-fighting antibodies that can remember infections when they return.

The researchers will use the grant to investigate the mechanism behind the effect of IL-35 on the immune system in pancreatic cancer, and to identify treatment targets at which to direct a combination of current and novel immunotherapies.

“We have identified IL-35-producing B cells as important regulators of anti-tumor immune responses in pancreatic cancer,” Pylayeva-Gupta said. “Our proposed research will shed light on the mechanisms by which these cells elicit pancreatic tumor growth and will provide us with novel therapeutic targets that could be used to synergize with existing immunotherapeutic approaches.”