How Smoking Fuels Pancreatic Cancer Growth and Worsens Outcomes: Study Finds Out

A new study published in Cancer Discovery, a journal of the American Association for Cancer Research, sheds light on why smokers have a higher risk of developing pancreatic cancer and experience worse outcomes compared to nonsmokers. Researchers from the University of Michigan Health Rogel Cancer Center have identified a specific immune pathway triggered by cigarette toxins that drives aggressive tumor growth. The study focused on how a chemical commonly found in cigarettes and other environmental pollutants influences pancreatic tumors. Researchers gave this chemical to mice with pancreatic cancer to observe its effects on Interleukin-22 (IL22), a protein previously linked to the tumor microenvironment. The research team discovered that a unique receptor on IL22-producing cells binds to these chemical toxins, not to naturally occurring proteins. The toxins then trigger IL22 release, which in turn fuels tumor progression. Notably, in mice lacking an immune system, the toxins failed to promote tumor growth—highlighting the immune system's central role in the process. Digging deeper, the team identified a subset of immune cells known as T-regulatory (Treg) cells as key players. These cells not only produce IL22 but also suppress the body’s natural anti-tumor response. “These T-regulatory cells can both make IL22 but also massively suppress any anti-tumor immunity. It’s a two-pronged attack,” said Timothy L. Frankel, M.D., co-director of the Rogel and Blondy Center for Pancreatic Cancer and Maud T. Lane Professor of Surgical Oncology at Michigan Medicine. When researchers removed these Treg cells, tumor growth driven by cigarette toxins was reversed. The findings were validated in human immune cells and pancreatic cancer tissues. Smokers with pancreatic cancer had significantly higher levels of Treg cells compared to nonsmokers. Encouragingly, an experimental drug that blocks the cigarette toxin showed effectiveness in shrinking tumors. The study also highlights the importance of tailored treatment based on smoking history and calls for improved screening strategies for high-risk individuals. More research is needed to explore therapeutic options that target this pathway.