Mouse experiments show cancers strip away the reactive oxygen signals T cells need to attack, and removing the antioxidant made some resistant tumors respond to treatment

Antioxidants are usually cast as health heroes — but some tumors use one as a shield. Researchers at the University of Cambridge and Oregon Health & Science University found that cancer cells release large amounts of an antioxidant protein called peroxiredoxin 1, or PRDX1, which mops up the reactive oxygen molecules that immune T cells need to switch on. The study appeared in Science.

When the team removed PRDX1 from mouse tumors, immune activity rose, and tumor growth slowed. Some tumors that had resisted immunotherapy began to respond.

The findings matter for the many patients whose cancers do not respond to today's immunotherapy drugs. Checkpoint inhibitors, which block brake signals such as PD-1 and PD-L1 on immune cells, have transformed treatment for melanoma, lung cancer, and other tumors, but many patients see little benefit or develop resistance. They do not mean dietary antioxidants or supplements cause cancer, and the researchers stress that people should not change their diets or treatments based on this work.

T Cells Need a Spark That Tumors Smother

Reactive oxygen species, a group that includes so-called free radicals, are often described simply as damaging byproducts of metabolism. But T cells, the immune system's tumor killers, need small bursts of these molecules to activate.

"We tend to think of reactive oxygen species purely as damaging byproducts of metabolism," said first author Xan Wesolowski of Cambridge's Department of Pathology, according to the University of Cambridge.

The team analyzed the fluid surrounding cells inside mouse tumors and found it had unusually strong antioxidant activity. PRDX1 stood out. By removing reactive oxygen from the tumor's surroundings, it deprived T cells of the activation signal, effectively smothering them chemically.

Mouse Experiments Restored the Immune Attack

Using CRISPR gene editing, the researchers made mouse cancer cells that could not produce PRDX1. Without it, T cells became more active, and tumors grew more slowly across several experimental models.

In one melanoma model, tumors lacking PRDX1 were rejected outright by the immune system, Pharmacy Times reported. In others, removing the protein made previously resistant tumors respond to immune checkpoint inhibitors, drugs that release the brakes on T cells. Depleting T cells erased the benefit, confirming the effect ran through the immune system.

The team also found that cancer cells ramp up PRDX1 as they evolve under immune pressure, suggesting it is one of the tools tumors acquire to escape.

Evidence From Human Tumors, With Limits

The researchers looked for the same mechanism in people using three approaches: data on proteins released by human cancer cell lines, gene activity across thousands of human tumors, and fluid collected from tumors removed during surgery. All three suggested human cancers also release PRDX1.

That evidence is supportive but indirect — and it stops short of showing a treatment effect in people. Harvard Medical School oncologist Ilyas Sahin, who was not involved, summarized it on X: "Human data were supportive but limited," according to OncoDaily.

The core results come from mouse models, and it is not yet clear which human cancer types rely most on this pathway or whether PRDX1 levels could predict who will respond to immunotherapy. No PRDX1-targeting treatment has been tested in patients. The study was published in September and highlighted again this month by ScienceDaily.

Not a Verdict on Vitamins or Antioxidant Supplements

The study helps explain a long-standing puzzle. Several large randomized trials found that antioxidant supplements did not prevent cancer, and some were linked to worse outcomes. If T cells depend on reactive oxygen signals, flooding the body with antioxidants could, in theory, blunt immune attacks.

But the study examined an antioxidant protein produced by tumors and concentrated in their immediate surroundings, not vitamins, fruits, vegetables or supplements. It does not show that eating antioxidant-rich foods is harmful, and those foods remain part of healthy diets. People with cancer should discuss any supplements with their oncology team, since some can interact with treatment.

"The immune system has already shown us that it can eradicate advanced cancers in some patients," Eil said, according to ecancer. The question is how to extend that success to tumors that currently resist treatment. Earlier work from the Cambridge group found that T cells engineered to produce more of their own reactive oxygen, through an enzyme called NOX2, attacked tumors more effectively in mice, one hint at how cell therapies might be armored against the antioxidant shield.

Senior author Rahul Roychoudhuri said blocking the process made tumors that ignore some immunotherapies start responding, calling it a pathway worth targeting. Possible approaches include drugs that neutralize tumor-released PRDX1, treatments that boost reactive oxygen signals inside tumors, and engineered T cells that resist the antioxidant shield. Robert Eil of OHSU suggested that prooxidants, not antioxidants, might one day help kick-start T cells.

The next step is testing those strategies in more cancer models before any human trial.

What Readers Want to Know

What did the study find? Tumors release the antioxidant protein PRDX1, which removes reactive oxygen molecules that T cells need to activate.

What happened when PRDX1 was removed? In mice, T cells became more active, tumors grew more slowly, and some resistant tumors responded to immunotherapy.

Does this apply to people? Human tumor data suggest cancers release PRDX1, but the treatment effects were shown only in mice.

Should I stop eating antioxidant-rich foods? No. The study did not examine diet, and those foods remain part of a healthy diet.

What about antioxidant supplements? The study does not prove supplements cause cancer. Patients should discuss supplements with their care team.

When could a treatment be available? Not soon. PRDX1-targeting therapies have not yet been tested in patients.