Researchers at the University of Michigan have discovered how smoking increases the aggressiveness of pancreatic cancer.
Researchers from the University of Michigan Health Rogel Cancer Center have made a significant breakthrough in understanding why smokers are at a higher risk for pancreatic cancer and why their prognosis tends to be worse than that of nonsmokers.
The findings, published in the journal Cancer Discovery, reveal a cellular mechanism that could pave the way for more targeted treatments.
The study identifies how chemicals found in cigarettes and other environmental toxins bind to a specific type of cell, leading to the production of a protein called interleukin-22 (IL22). This protein results in more aggressive tumor growth in mice with pancreatic cancer.
The researchers found that a particular immune cell, known as the T-regulatory cell, exacerbates this effect by both producing IL22 and suppressing the body’s anti-tumor immunity.
A Two-Pronged Attack on the Immune System
“It dramatically changed the way the tumors behave. They grew much bigger, they metastasized throughout the body. It was really quite dramatic,” senior author Timothy L. Frankel, a co-director of the Rogel and Blondy Center for Pancreatic Cancer and the Maud T. Lane Professor of Surgical Oncology at Michigan Medicine, said in a news release.
The team discovered that when these T-regulatory cells were removed, the chemical-induced tumor growth was inhibited.
Confirming their results in human cells, the researchers found that smokers with pancreatic cancer had more T-regulatory cells than their non-smoking counterparts.
Pathway to Potential Treatments
The researchers further demonstrated that an inhibitor blocking the cigarette chemical was effective in reducing tumor size.
This insight opens the door to new treatment strategies that could deactivate these super-suppressive cells and unlock the body’s natural anti-tumor immunity, potentially enhancing the efficacy of existing immunotherapies, which have not been very successful in treating pancreatic cancer due to the immunosuppressive environment.
“If we are able to inhibit the super suppressive cells, we might also unlock natural anti-tumor immunity. This could be even further activated by current immunotherapies, which do not work well in pancreatic cancer because of the immunosuppressive environment,” Frankel added.
Implications for Screening and Treatment
The research highlights the importance of considering personalized treatment based on a patient’s exposure to cigarette smoke.
“There’s a potential that we need to treat smokers who develop pancreatic cancer differently,” added Frankel said.
He also emphasized the need for heightened screening protocols for smokers, especially given that early detection tools for pancreatic cancer are limited.
A Call for Awareness
Pancreatic cancer signs include low back pain, yellowing of the skin and unexplained weight loss.
Frankel advises individuals with a family history of the disease or other pancreatic conditions to avoid smoking, emphasizing the cancer’s high mortality rate and the urgent need for preventive measures.
Moving Forward
More research is needed to evaluate the therapeutic potential of drugs that inhibit these environmental toxins or block their signaling pathways. With further study, these findings could revolutionize how pancreatic cancer is treated and diagnosed, particularly in smokers who are already at a greater risk.
Source: Michigan Medicine