For a long time, vitamin A has been treated as a symbol of good health, a nutrient we rarely question. It helps our vision, supports the body’s natural defences, and is essential for healthy growth. Because of these benefits, scientists have believed that it might help protect us from cancer. But new research from Princeton University tells a more uneasy story. The findings suggest that vitamin A’s relationship with cancer is complex. Instead, it may play a far more complex, and in some cases troubling, role – a reminder that even familiar nutrients can behave unexpectedly inside the human body.
Researchers at the Princeton branch of the Ludwig Institute for Cancer Research have uncovered evidence that a byproduct of vitamin A, called all-trans retinoic acid, can actually help tumours evade the immune system. Rather than strengthening the body’s natural defences, this molecule appears to quietly suppress them, allowing cancer to grow undetected. The discovery not only helps explain years of conflicting evidence around vitamin A and cancer but also points toward a promising new way to strengthen cancer immunotherapy.
At the heart of the research are dendritic cells, a critical part of the immune system. Sentinel cells patrol the body for signs of disease and alert T cells when they detect a threat. Dendritic cells are so important that they are often used to create experimental cancer vaccines, where they are “trained” in the lab to recognise tumour markers and then returned to the patient to trigger an immune attack.
Yet despite their promise, dendritic cell vaccines have repeatedly fallen short in clinical trials. Until now, scientists did not fully understand why.
The Princeton team discovered that during the process of making these vaccines, dendritic cells begin producing large amounts of retinoic acid. This vitamin A derivative alters the cells from within, preventing them from fully maturing and weakening their ability to activate cancer-killing T cells. Essentially, the immune system’s mobilising cells become passive.
Even more concerning, retinoic acid doesn’t stop there. Furthermore, retinoic acid modifies the tumour environment by fostering immune cells that are less effective in combating cancer, thereby shifting the balance further in favour of tumour growth. This creates what researchers describe as a dangerous “immune tolerance”, a state in which the immune system sees cancer but no longer responds to it with urgency.
Crucially, the researchers didn’t just identify the problem; they found a solution.
The team developed an experimental drug, known as KyA33, that blocks the production of retinoic acid by both cancer cells and immune cells. In preclinical mouse studies, dendritic cell vaccines created in the presence of this inhibitor triggered far stronger immune responses. Tumour growth slowed, cancer onset was delayed, and in some cases the drug worked even when given on its own, acting as a standalone immunotherapy.
The research also helps solve a long-standing paradox. In laboratory experiments, vitamin A derivatives can cause cancer cells to stop growing or even die. Large human trials, however, have demonstrated a link between high vitamin A intake and increased cancer risk and mortality. The new findings suggest that while cancer cells may become resistant to vitamin A’s direct effects, the immune system does not. Instead, tumours exploit retinoic acid to weaken immune surveillance, allowing cancer to progress unchecked.
By designing drugs that safely and selectively shut down this pathway, the researchers believe they have opened the door to an entirely new class of cancer treatments – ones that restore the immune system’s ability to do what it was meant to do.
The implications could extend beyond cancer. Conditions like cardiovascular disease and diabetes also implicate retinoic acid signalling, suggesting a broader therapeutic use for these inhibitors.
For now, the work remains at the preclinical stage. But by revealing how a common nutrient can be hijacked by cancer and how that process can be blocked, the research offers renewed hope for more effective cancer vaccines and immune-based therapies in the future.
