A simple supplement could help your immune system fight cancer and viral infections

A common amino acid found in everyday foods could play a surprisingly important role in helping the immune system recognize cancer and fight viral infections. Scientists at Rockefeller University have discovered that when the body runs low on arginine, a key part of its immune defense system can stop working properly, potentially allowing dangerous cells and viruses to escape detection. Arginine is an amino acid that the body produces naturally and also obtains from protein-rich foods. It is essential for making proteins that perform countless functions throughout the body. Researchers have long known that unusually low arginine levels are associated with several diseases, including colon cancer, but exactly how this shortage affects the body's defenses has remained unclear. Now, new research suggests that restoring arginine levels could help the immune system respond more effectively to serious threats. In experiments involving mice, increasing dietary arginine reduced the formation of colon cancer tumors and lessened the severity of influenza and SARS-CoV-2 infections. Remarkably, providing arginine after mice had already contracted influenza also improved their outcomes. The findings, published in the journal Cell, raise the possibility that an inexpensive, readily available supplement could eventually become a useful addition to cancer treatments and strategies for combating viral infections. However, further research in humans is needed to determine whether the benefits observed in mice translate into effective treatments for people. How a Missing Nutrient Could Help Cancer Escape the Immune System The research was led by Sohail Tavazoie, who directs the Elizabeth and Vincent Meyer Laboratory of Systems Cancer Biology at Rockefeller University. His team has spent years investigating how arginine influences cancer development and progression. In 2023, the researchers discovered that depriving colon cancer cells of arginine caused them to accumulate more genetic mutations. These changes can contribute to the unpredictable behavior of cancer cells, raising important questions about how arginine shortages might influence the disease. The latest study reveals another potentially significant consequence. When arginine becomes scarce, cells struggle to produce enough of a crucial immune system protein known as MHC-1. This protein acts as a warning system, helping immune cells identify potential dangers such as cancerous changes or viral infections. Without enough MHC-1, abnormal or infected cells may become harder for the immune system to recognize. Encouragingly, the researchers also found that supplying a moderate amount of arginine, comparable to the quantity available in a couple of over-the-counter supplement tablets, could help restore production of this important protein. "Our work reveals how a lack of arginine interferes with the immune system, and suggests that upping arginine intake could prove beneficial," says first author Qiushuang Wu, a postdoc in the lab. "Perhaps that means it could be used in combination with other therapies to treat both cancer and viral infections." "Arginine supplementation could be readily tested in patients receiving immunotherapies or given to high-risk populations exposed to viral pathogens," Tavazoie suggests. "Considering that arginine is inexpensive and readily available, we hope that therapeutic and preventative studies could be undertaken soon." The Surprising Connection Between Arginine and Immune Defenses To understand why arginine has such an important effect, the researchers investigated how cells use amino acids to manufacture proteins. Proteins are built from amino acids according to genetic instructions encoded in DNA. These instructions are copied into messenger RNA, which carries the information to the cellular machinery responsible for protein production. The instructions are read in groups of three genetic letters called codons. Each codon specifies an amino acid or provides another signal needed during protein production. Arginine is unusual in that six different codons can specify it, reflecting the multiple ways its incorporation into proteins can be encoded. Scientists already knew that changes in amino acid availability could affect cellular metabolism and signaling, two processes that help regulate how cells obtain energy and respond to their surroundings. What remained less clear was whether shortages of particular amino acids could directly influence which proteins cells produce. To investigate, Wu examined the effects of arginine availability across several disease models, including colon cancer, influenza, and SARS-CoV-2. Each of these diseases has previously been associated with abnormal levels of various amino acids. The research was supported in part by the Stavros Niarchos Foundation (SNF) Institute for Global Infectious Disease Research at The Rockefeller University and the Weill Cancer East Hub. "One of the most dramatic patterns to emerge was that arginine was the most depleted amino acid in all of these diseases," she says. Why Low Arginine Levels Can Disrupt the Immune System In laboratory experiments using cultured cells, Wu examined how arginine shortages affected protein production. She identified 414 proteins whose levels dropped abnormally when arginine was scarce. Many of these proteins were associated with biological functions already known to depend on arginine. However, the researchers uncovered a more unexpected effect involving three genes from the HLA family. These genes provide instructions for producing proteins associated with MHC-I (major histocompatibility complex class I), an essential component of the immune system's ability to recognize threats. MHC-I proteins are displayed on the surfaces of cells throughout the body. They act somewhat like identification displays, presenting small fragments of proteins from inside the cell to immune cells known as T cells. When these displays reveal suspicious material, such as proteins produced by a virus or abnormal proteins associated with cancer, T cells can recognize the danger and help coordinate an immune response. But the researchers found that arginine deficiency interfered with the production of these molecular warning signals. The reason involved ribosomes, the tiny cellular machines that assemble proteins by following genetic instructions. Because the proteins involved in MHC-I production require arginine at numerous points, the researchers suspected that an insufficient supply could interfere with their assembly. Further experiments confirmed that suspicion. When arginine was unavailable, ribosomes stalled while trying to manufacture MHC-I proteins. Without enough of the required amino acid, the cells could not efficiently complete the process. As a result, fewer MHC-I proteins reached the cell surface, reducing the signals that would normally alert T cells to cancer-associated or viral proteins. This created an opportunity for dangerous cells to avoid immune detection. "These findings are exciting because they reveal that consumption of a specific amino acid can directly regulate gene expression in an organism by increasing production of a protein enriched in that amino acid," Tavazoie says. "We believe that such selective translational tuning of gene expression through dietary manipulation likely extends to many other proteins and amino acids." More Arginine Meant Fewer Colon Cancer Tumors in Mice After identifying the molecular mechanism, Wu investigated whether changing the amount of arginine in an animal's diet could influence disease outcomes. The results were striking. Mice receiving diets low in arginine developed more colon cancer tumors. In contrast, mice consuming higher amounts of the amino acid developed fewer tumors. These findings provided evidence that arginine availability can influence cancer development through its effects on the immune system, rather than simply changing how individual cancer cells behave. The results also raised a broader question: If arginine helps immune cells recognize cancer, could it provide similar benefits when the body encounters dangerous viruses? Arginine Also Improved Outcomes From Influenza and COVID-19 Viruses To explore that possibility, Wu collaborated with Heinz-Heinrich Hoffman, a research assistant professor in Charles Rice's Laboratory of Virology and Infectious Disease. Together, they examined the effects of dietary arginine in mouse models of influenza and SARS-CoV-2, the virus responsible for COVID-19. The findings followed the same general pattern seen in the colon cancer experiments. Mice consuming more arginine experienced less severe symptoms from viral infections, suggesting that adequate levels of the amino acid helped support the body's immune defenses. The researchers then made an even more surprising discovery. Arginine did not appear to be beneficial only when consumed before an infection. Giving mice additional arginine after they had already been infected with influenza also improved their outcomes. "Not only did mice with an arginine-rich diet have milder symptoms from viral infections, giving the mice arginine after influenza infection improved their outcomes too," Wu notes. "That was very surprising. From our genetic models, we knew manipulating arginine levels had a strong effect on gene expression, but we didn't expect the dietary manipulation to be equally impactful." The observation suggests that changing nutrient availability might influence how the immune system responds even after a viral infection has taken hold. Could a Simple Supplement Improve Cancer and Virus Treatments? The discovery has potentially important implications for understanding why some people become more vulnerable to cancer and severe viral infections. Arginine levels naturally decline with age, and inadequate nutrition can further reduce the amount available to cells. The researchers suspect that these changes may contribute to the weakening of immune defenses seen in certain diseases and in older adults. "Qiushuang's findings illuminate how poor diet and aging -- during which arginine levels naturally decline -- could create the perfect storm for the initiation of colon cancer. Similarly, age-related arginine loss could partially contribute to the greater mortality caused by respiratory viruses," Tavazoie says. "We're also investigating whether making dietary changes in other amino acids has beneficial effects in a variety of disease contexts. There are no doubt more discoveries to come." The possibility of using arginine alongside existing cancer immunotherapies is particularly intriguing. These treatments work by helping the immune system recognize and attack cancer cells. If low arginine levels interfere with the molecular signals required for that recognition, restoring the nutrient might help some treatments work more effectively. The researchers also see potential for investigating arginine supplementation in people at elevated risk of respiratory viral infections. For now, these possibilities remain experimental. The findings do not establish that taking arginine supplements prevents or treats cancer, influenza, or COVID-19 in humans. Nevertheless, the research reveals an important connection between nutrition and immunity. Rather than simply providing the raw materials needed to build proteins, specific amino acids may help determine how effectively the body's immune defenses identify and respond to dangerous threats. And because arginine is inexpensive and widely available, the discovery could provide a practical starting point for future studies aimed at strengthening the immune system against cancer and infectious diseases.