Common vitamin byproduct may help cancer evade immune system, study finds
A substance the body makes from vitamin A can make the immune system less effective at fighting cancer, a new study reveals.
Vitamin A itself is an essential nutrient, but one of its byproducts can accidentally "turn off" parts of the immune response against cancer, according to new research published in Nature Immunology.
Blocking that byproduct’s effects can restore immune activity and may improve cancer immunotherapy, the findings suggest.
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Researchers at the Princeton University Branch of the Ludwig Institute for Cancer Research made this discovery by growing dendritic cells, key immune cells that activate the body’s defenses, in a lab.
As these cells developed, the scientists noticed they naturally turned on an enzyme that makes retinoic acid, a molecule that comes from vitamin A.
Retinoic acid can weaken dendritic cells' ability to stimulate immune responses. This reduces the effectiveness of dendritic cell vaccines, an immunotherapy that trains the immune system to attack cancer, according to the study.
The researchers also found that when dendritic cells made a lot of the retinoic acid, they were less able to send strong danger signals to the immune system.
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When they removed the retinoic acid, the dendritic cells became stronger and better at activating T cells, which are the immune system’s cancer-killing cells.
A second study, published in iScience by collaborators from the same research group, looked at how to develop drugs to block this process.
Using computer modeling and large drug screens, the team designed and identified small molecules that blocked the enzymes that produce retinoic acid.
This led to the creation of a promising inhibitor that shuts down retinoic acid production in a controlled way, the same tool used in the first study’s experiments, the researchers noted.
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"Taken together, our findings reveal the broad influence retinoic acid has in attenuating vitally important immune responses to cancer," lead researcher Yibin Kang said in a press release.
"In exploring this phenomenon, we also solved a long-standing challenge in pharmacology by developing safe and selective inhibitors of retinoic acid signaling and established preclinical proof of concept for their use in cancer immunotherapy."
As these findings are based on laboratory and animal models, they may not fully reflect how retinoic acid functions in humans.
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Also, the studies examined a specific vitamin A-derived molecule (retinoic acid) acting in immune cells, not dietary vitamin A intake or overall vitamin A status.
Vitamin A remains an essential nutrient for normal immune function, growth and vision, according to the National Institutes of Health, and extensive human studies have found no evidence that vitamin A causes cancer.