Vitamin A May Help Cancer Evade the Immune System, Study Finds

By Oladapo Anjolaoluwa 

Scientists at the Princeton University branch of the Ludwig Institute for Cancer Research have discovered that a molecule derived from vitamin A may help cancer evade the body’s immune defenses. The molecule, known as all-trans retinoic acid, was found to weaken natural anti-cancer immune responses and, in some cases, reduce the effectiveness of cancer vaccines.
The findings, published in Nature Immunology and iScience, help explain long-standing debates about vitamin A’s mixed effects on health and disease. They also led to the development of experimental drugs that block retinoic acid signaling, opening new possibilities for cancer immunotherapy.
In the Nature Immunology study, led by researcher Yibin Kang and graduate student Cao Fang, scientists found that retinoic acid produced by dendritic cells—immune cells that activate the body’s defenses—can reprogram these cells to tolerate tumors instead of attacking them. This immune tolerance significantly reduces the effectiveness of dendritic cell vaccines, a form of immunotherapy designed to train the immune system to recognize cancer.
The researchers discovered that during the laboratory process used to produce dendritic cell vaccines, the cells begin producing high levels of retinoic acid. This suppresses their maturation and weakens their ability to trigger strong anti-tumor immune responses, which may explain why such vaccines often perform poorly in clinical trials.
To counter this effect, the team developed an experimental drug called KyA33, which blocks the production of retinoic acid. In animal studies, dendritic cell vaccines created in the presence of KyA33 generated stronger immune responses, delayed tumor development, and slowed cancer progression. When administered alone, the drug also reduced tumor growth by boosting immune activity.
A second study, published in iScience and led by former graduate student Mark Esposito, focused on designing drugs that shut down retinoic acid signaling entirely. Using computational modeling and large-scale drug screening, the researchers overcame decades-long challenges in targeting this pathway, leading to the development of KyA33.
The studies also help resolve a paradox surrounding vitamin A and cancer. While retinoic acid can slow cancer cell growth in laboratory experiments, large clinical trials have shown that high vitamin A intake may increase cancer risk and mortality. The researchers found that cancer cells often produce retinoic acid but lose their ability to respond to its growth-limiting effects. Instead, the molecule primarily suppresses immune responses in the tumor environment, allowing cancer to grow unchecked.
“These findings reveal the broad influence retinoic acid has in weakening vital immune responses to cancer,” Kang said. “By safely inhibiting this pathway, we’ve opened the door to a new approach in cancer immunotherapy.”
Kang and Esposito have since launched a biotechnology company, Kayothera, to advance these experimental drugs into clinical testing, with the goal of developing new treatments for cancer and other diseases influenced by retinoic acid.