There are major efforts underway to harness the power of immunotherapy – training the patient’s own immune system to recognize and attack cancer cells – to improve outcomes for pancreatic cancer patients. But before immunotherapy’s potential can be fully realized, it’s critical to understand the roles the immune system and inflammatory responses play in the development and progression of the disease.
In her first published paper as an independent investigator, two-time Pancreatic Cancer Action Network (PanCAN) grantee Florencia McAllister, MD, and her colleagues sought to understand how chronic pancreatitis, or constant inflammation of the pancreas, conferred an increased risk of developing pancreatic cancer.
The research team zeroed in on a small protein called interleukin 17 (IL17) that is secreted by immune cells to induce and maintain inflammation.
“We demonstrate that IL17 is secreted by immune cells that are recruited to the pancreas during chronic pancreatitis,” described McAllister, assistant professor in the departments of clinical cancer prevention and gastrointestinal medical oncology at MD Anderson Cancer Center in Houston. “And then IL17 secretion is capable of turning on genes in normal pancreas cells that are typically expressed in embryonic stem cells, like Dclk1 and POU2F3, which are also markers of tuft cells that may be involved in cancer initiation.”
She added: “Our new understanding of IL17’s role in promoting tumorigenesis mechanistically links pancreatic inflammation with cancer initiation and progression. Moreover, we found that some of the genes that get activated as a result of IL17 secretion are associated with poor prognosis in patients with pancreatic cancer.”
Now that IL17 has been identified as a culprit linking an inflammatory, immune response with tumor initiation, McAllister and her colleagues will work to deepen their understanding of IL17’s role, learn more about its target genes and determine whether IL17’s activity can be therapeutically modulated – all with the goal to improve pancreatic cancer patient outcomes.
The Gastroenterology paper describing this work cites McAllister’s Career Development Award from PanCAN as a primary funding source, which came after she received a Fellowship Award during her postdoctoral training. In addition to receiving research funding from PanCAN, McAllister benefited by becoming a part of the organization’s Community for Progress, which provides opportunities for data-sharing and collaboration-building to support scientists and their careers.
McAllister explained, “I met two of the co-authors on the paper, Drs. Tim Wang and Paul Chiao, through PanCAN events where we attended as fellow grant recipients. They have become key collaborators for me, providing experimental guidance and expertise toward our collective research aims.”
And for McAllister, the fight is personal – she lost her mother to pancreatic cancer in 2008. “PanCAN research grants,” she said, “have been fundamental for my transition from fellowship into junior faculty and for allowing me to focus my scientific career on pancreatic cancer research.”