For years, scientists knew that something was wrong with cells in cancer patients and people with serious viral infections — their bodies were running low on a substance called arginine. But nobody understood exactly why that mattered. Now, researchers at Rockefeller University in New York think they have found an answer, and it could change how we treat diseases like colon cancer, influenza, and even COVID-19.
Arginine is an amino acid — one of the building blocks that cells use to create proteins. The body makes it naturally, and people also get it from foods like meat, nuts, and dairy. When arginine levels drop in people who are sick, something important breaks down inside their cells.
Sohail Tavazoie leads the Elizabeth and Vincent Meyer Laboratory of Systems Cancer Biology at Rockefeller. His team has been studying the link between low arginine and disease for years. In their newest research, published in the journal Cell, they discovered that when arginine runs short, cells can no longer make enough of a protein called MHC-1. This protein sits on the surface of cells like a little flag, warning the immune system about threats — whether it is a mutated cancer cell or a virus sneaking inside.
"Without that flag, dangerous cells slip past the immune system's defenses unnoticed," said Qiushhuang Wu, a postdoctoral researcher in Tavazoie's lab and the study's first author.
The researchers examined what happened when they cut arginine levels in cell cultures. They found that 414 different proteins became unusually low. But the most surprising discovery involved three genes that control MHC-1 production. When arginine was scarce, the cellular machines that build proteins — tiny structures called ribosomes — simply stopped mid-work. They could not finish making MHC-1 without enough arginine. Fewer flags on the cell surface meant fewer warnings sent to T cells, the immune system's attack squad.
The team tested the idea in mice. Animals that ate low-arginine diets developed more colon cancer tumors. Mice that received extra arginine developed fewer tumors. The pattern was clear.
The researchers studied three disease models: colon cancer, influenza, and SARS-CoV-2. In all three, arginine was the amino acid most depleted in patients' bodies.
The good news? The team found that a moderate amount of arginine — roughly what someone might get from a couple of over-the-counter tablets — could restore the genes involved in MHC-1 production. If this works in humans, it could be a simple and affordable addition to existing treatments.
"Arginine supplementation could be readily tested in patients receiving immunotherapies or given to high-risk populations exposed to viral pathogens," Tavazoie said. "Considering that arginine is inexpensive and readily available, we hope that therapeutic and preventative studies could be undertaken soon."
The lab is now working with collaborators to explore how this discovery might be used to help patients.