Study: Arginine Shortage May Hinder Immune Detection of Cancer and Viruses
Rockefeller University researchers found in mice that low levels of the amino acid arginine reduce production of a protein key to immune recognition, while extra arginine lowered colon cancer tumor numbers and eased viral infections. Human studies are still needed.
Researchers at Rockefeller University in New York have reported in the journal Cell that a shortage of the amino acid arginine can impair the immune system's ability to recognize cancer cells and virus-infected cells. In experiments on mice, higher arginine intake reduced the formation of colon cancer tumors and lessened the severity of influenza and SARS-CoV-2 (the virus that causes COVID-19) infections. The work is at an early stage, and its findings still have to be confirmed in humans.
Arginine is an amino acid that the body makes itself and also gets from protein-rich foods. Unusually low levels are known to be linked with several diseases, including colon cancer, but how the deficit affects the body's defenses had been unclear.
How the mechanism works
The study was led by Sohail Tavazoie, head of the Elizabeth and Vincent Meyer Laboratory of Systems Cancer Biology at the university. First author Qiushuang Wu, a postdoctoral researcher, identified 414 proteins whose levels fell abnormally in cultured cells when arginine was scarce. Among them were three genes from the HLA family, which govern production of MHC-I proteins. These proteins display small fragments of proteins from inside a cell to T cells, a type of immune cell, allowing the immune system to spot signs of a virus or cancer.
Because building MHC-I proteins requires arginine at many points, ribosomes, the cellular machines that assemble proteins, stalled when it was missing. Fewer of these proteins reached the cell surface, making it easier for dangerous cells to go unnoticed.
Results in mice
Mice fed diets low in arginine developed more colon cancer tumors, while those on higher-arginine diets developed fewer. Working with virologist Heinz-Heinrich Hoffman, the team found that mice receiving more arginine had milder symptoms of influenza and SARS-CoV-2. Giving arginine after influenza infection also improved outcomes.
The authors note that arginine levels decline with age and suggest this may contribute to weakened immune defenses. Tavazoie said arginine supplementation could soon be tested in patients receiving immunotherapy or in high-risk groups. The results do not show that arginine supplements prevent or treat cancer, influenza or COVID-19 in people.
