Free radicals are traditionally associated with damage to cells in the body, leading to widespread interest in whether antioxidants could help prevent cancer. But new research suggests that these often misunderstood molecules also play an important role in protecting us against disease.
Scientists have discovered that some immune cells actually need small amounts of reactive oxygen species, a group of molecules that include free radicals, to recognize and destroy cancer cells. Even more surprising, tumors appear to exploit this need by releasing natural antioxidants that interfere with the immune system’s ability to fight back.
The results, published in the journal Sciencereveal a previously unknown way in which cancer evades the body’s defenses. They could also point toward new strategies aimed at making cancer immunotherapies more effective, particularly in patients whose tumors are resistant to existing treatments.
How Cancer Uses Antioxidants to Disable Immune Cells
The immune system protects the body by identifying and eliminating threats, ranging from harmful bacteria and viruses to abnormal cells that can develop into cancer. Among its most important defenses are specialized immune cells called T cells, which can recognize and destroy tumor cells.
However, these anti-cancer cells rely on chemical signals to activate their destructive capabilities. Small amounts of reactive oxygen species provide some of these signals, helping T cells go into attack mode.
Researchers from the University of Cambridge in the UK and Oregon Health and Science University in the US have found that tumors can interfere with this process. By examining the fluid surrounding cells inside tumors grown in mice, they found that cancer cells create chemical conditions that effectively prevent neighboring T cells from activating.
The key is a natural antioxidant protein called Peroxiredoxin 1 (PRDX1). Cancer cells release large amounts of this protein into their environment, where it removes reactive oxygen species that T cells need to function. Without these activating signals, immune cells become less effective at destroying cancer.
This is because tumors use antioxidants as a chemical shield, weakening the immune response that would otherwise threaten their survival.
Removing Cancer’s Antioxidant Shield Slows Tumor Growth
To determine whether this defense mechanism could be disrupted, researchers used CRISPR gene editing to modify cancer cells in mice. The modified cells could no longer produce PRDX1, allowing the team to examine what happened when tumors lost their ability to release the antioxidant protein.
The results were encouraging. Without PRDX1, immune cells became more active and tumor growth was reduced. This suggests that interfering with the antioxidant protein could restore some of the immune system’s ability to attack cancer.
The researchers then studied whether human cancers used the same strategy. They reviewed existing data on proteins released by human cancer cell lines, studied patterns of gene activity in thousands of human tumors, and analyzed fluid collected from tumors surgically removed from patients.
All three pieces of evidence supported the same conclusion. Human cancers also release PRDX1 into the environment, where it can eliminate the reactive oxygen species that anticancer T cells depend on.
Dr Xan Wesolowski, one of the lead authors from the Department of Pathology at the University of Cambridge, explained why this discovery challenges conventional thinking about these molecules.
“We tend to think of reactive oxygen species only as harmful byproducts of metabolism. But we increasingly understand that they have important functions within cells, and T cells need them to activate. Our study expands on this picture, revealing that tumors can exploit this very dependence to evade elimination.”
A new strategy to make cancer immunotherapy more effective
Cancer treatment increasingly aims to help the immune system recognize and eliminate malignant cells. These approaches, known as immunotherapies, have produced remarkable results for some patients, but many others experience little or no benefit.
New research identifies a possible reason why some tumors may resist immune attacks. By releasing PRDX1, cancer cells can suppress the T cells that immunotherapies are supposed to activate.
Importantly, researchers found that preventing cancer cells from producing this antioxidant improved their response to immunotherapy in experimental models. Some tumors that had previously been resistant to treatment became reactive when antioxidant defense was disrupted.
Professor Rahul Roychoudhuri, also from Cambridge’s Department of Pathology, said the results identified a promising target for future cancer treatments.
“We’ve found a new way in which cancers inhibit the immune system. When we block this process, tumors that don’t respond to certain immunotherapies begin to respond to treatment. This tells us that this is a pathway worth targeting therapeutically, and there are several ways to do this.”
This discovery also raises the possibility of using another type of chemical approach to boost the immune response.
Dr. Robert Eil of the Oregon Health and Science University School of Medicine said: “Our study suggests a possible way to boost T-cell immunotherapies. Rather than using antioxidants, it could be that prooxidants can restart the action of T cells against tumor cells. »
Why the findings raise questions about antioxidant supplements
Beyond their potential implications for cancer treatment, the findings could help explain a long-standing conundrum regarding antioxidant supplements.
Antioxidants have often been promoted for their ability to neutralize reactive oxygen species and protect cells from damage. Since these molecules may contribute to processes associated with cancer development, researchers studied whether taking antioxidant supplements could reduce cancer risk.
However, several large randomized clinical trials have failed to demonstrate such protection. In some cases, antioxidant supplementation has even been linked to worse outcomes.
The new findings suggest a possible explanation. Although reactive oxygen species can damage cells, they also help activate immune defenses that fight cancer. Removing too many of these molecules could unintentionally interfere with the immune system’s ability to recognize and destroy tumors.
This does not establish that antioxidant supplements generally promote cancer, but it highlights the importance of understanding how these molecules behave in different biological contexts.
The researchers also emphasize that their experimental results remain preclinical. Although they identified evidence for the same antioxidant mechanism in human cancers, potential treatment strategies have not yet been established as safe or effective in patients.
People living with cancer should therefore not change their diet, supplement use, or medical treatments based on these findings without consulting a healthcare professional.
The research was widely supported by the Medical Research Council, the European Research Council, Wellcome and the National Institutes of Health/National Cancer Institute.
Gn Health
