Common vitamin byproduct may help cancer evade immune system, study finds

A substance that the body produces from vitamin A may make the immune system less effective in 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.

The findings suggest that blocking the effects of that byproduct can restore immune activity and improve cancer immunotherapy.

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Researchers at Princeton University’s 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 the laboratory.

As these cells developed, scientists noticed that they naturally activated an enzyme that produces retinoic acid, a molecule that comes from vitamin A.

Retinoic acid may weaken the ability of dendritic cells 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 produced a large amount of retinoic acid, they were less able to send strong danger signals to the immune system.

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When they removed retinoic acid, the dendritic cells became stronger and better at activating T cells, which are the cancer cells of the immune system.

A second study, published in iScience by collaborators from the same research group, analyzed how to develop drugs to block this process.

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Using computer models 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 stops retinoic acid production in a controlled manner — the same tool used in the experiments in the first study, the researchers noted.

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“Taken together, our findings reveal the broad influence that retinoic acid has in attenuating critically important immune responses to cancer,” lead researcher Yibin Kang said in a news release.

“By exploring this phenomenon, we also solved a long-standing challenge in pharmacology by developing safe and selective inhibitors of retinoic acid signaling and established a preclinical proof of concept for their use in cancer immunotherapy.”

Limitations of the study

As these findings are based on animal and laboratory models, they may not fully reflect how retinoic acid works in humans.

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Additionally, the studies examined a specific molecule derived from vitamin A (retinoic acid) that acts on 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.