- Prior research has linked smoking to pancreatic cancer, but the reasons why were unclear.
- A new mouse study shows that chemicals in cigarette smoke change the immune system, which may prevent the immune system from fighting tumors.
- These findings could open the door for new treatments targeting this mechanism, but in the meantime, experts say this is yet another reason to quit smoking.
It has long been understood that there was a link between smoking and pancreatic cancer, but the exact mechanism was unclear.
Now, a group of scientists has discovered that certain chemicals in cigarette smoke actually reprogram the immune system in a way that helps tumors grow and spread. This could point to new treatment strategies for pancreatic cancer, which currently has very few options.
According to the authors, their findings are significant because pancreatic cancer is one of the deadliest types of cancer, with only a five-year survival rate of 13%. The full results of the study were published on September 4 in Cancer Discovery.
In 2025 alone, it is estimated that more than 67,000 Americans will be diagnosed with pancreatic cancer, and nearly 52,000 will die from it.
The research, carried out by a team at the University of Michigan, combined lab experiments, mouse models, and human tissue samples.
They focused on a group of chemicals in cigarette smoke called aryl hydrocarbon receptor ligands (AhRLs).
These include well-known carcinogens such as dioxins. To mimic smoking, mice were treated with cigarette smoke extract or with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a powerful AhR ligand.
The researchers then implanted pancreatic cancer cells directly into the animals’ pancreases to track tumor growth.
They also used genetically engineered mice to tease apart how different immune cells responded to these smoke-related chemicals.
Finally, they compared the mouse findings to human pancreas tissue from organ donors and cancer patients.
The results were striking. Both cigarette smoke and TCDD accelerated pancreatic tumor growth in mice — but only if their immune system was intact. That means the chemicals weren’t damaging tumor cells directly. Instead, they were altering the immune response.
The key player was a receptor called AhR on CD4+ T cells. Once activated, these cells began producing more of a molecule called IL-22 and also boosted the number of regulatory T cells (Tregs).
Normally, Tregs keep the immune system in check. But in this case, they prevented CD8+ T cells — the ones that usually attack cancer — from doing their job. In other words, smoking tipped the balance of the immune system away from fighting tumors and toward letting them grow.
The team also saw that exposure to TCDD promoted early precancerous changes in the pancreas, suggesting that chemicals in cigarette smoke may play a role not just in cancer progression but also in its initiation.
Human tissue samples told a similar story. Smokers had more activation of the AhR pathway, and pancreatic tumors from smoking patients contained more Tregs.
The number of these suppressive cells also tracked with how much the patient had smoked over their lifetime.
According to the authors, what they have learned could potentially lead to new treatments that block AhR activation or reduce the suppressive effect of Tregs.
This could help the immune system mount a stronger anti-cancer response, especially in smokers.
They additionally note that, since AhR ligands are also found in pollutants and industrial chemicals, the findings may carry wider public health significance.
However, Asfar Azmi, PhD, director of the Pancreatic Cancer Research Initiative at the Barbara Ann Karmanos Cancer Institute, who was not involved in the study, urges caution in interpreting what the findings mean.
“Although this research represents an important step forward, it’s still early,” Azmi said, adding that much of the evidence comes from labs, animal studies, and findings from human tissues.
“That means the results show a mechanism linking smoking and pancreatic cancer, but they don’t prove that every smoker will develop this cancer, or that blocking this pathway will automatically prevent it,” he told Healthline.
Azmi noted that more clinical research is necessary before these findings will actually change doctors’ practices regarding the treatment of pancreatic cancer.
Najeeb Al Hallak, MD, MS, a medical oncologist with the Barbara Ann Karmanos Cancer Institute, said that “the message is clear that quitting smoking is one of the most important steps people can take to lower their risk of pancreatic cancer.” Hallak wasn’t involved in the study.
He further pointed out that smoking cessation may help reduce people’s risk of many other cancers, as well as heart and lung diseases.
“Even reducing exposure helps,” Hallak told Healthline, “but the greatest benefit comes from complete cessation.”
Hallak added that if you are a heavy smoker, it would also be a good idea to speak with your doctor about pancreatic cancer risk and whether you qualify for specialized monitoring or risk-reduction programs.
He also acknowledged the difficulties of smoking cessation, offering smokers some encouraging words. “Quitting is hard, but it is absolutely possible, and thousands succeed every day,” he said.
The first step in quitting? Speak with your personal physician. “They can guide you to nicotine replacement (patches, gum, or lozenges) or medications that reduce cravings,” Hallak said.
Hallak added that seeking support is essential. “Counseling, support groups, and quit lines (e.g., 1-800-QUIT-NOW) double your chances of success,” he said.
Additionally, Hallak suggests planning for your triggers. For example, if you are accustomed to smoking after meals or with coffee, create a healthier alternative that you can do instead.
Finally, he urges that you don’t give up after slips.
“Many people need several tries before quitting for good,” said Hallak. “Each attempt builds skills for the next.”