Free radicals have a bad reputation. For decades they have been described as damaging byproducts of metabolism, which is a large part of why antioxidant supplements became popular as a possible way to lower cancer risk. A study in Science adds a twist: some of the cells that fight cancer actually need these molecules to work, and tumors appear to take advantage of that.

T cells need a spark of reactive oxygen

T cells are immune cells that hunt down and destroy abnormal cells, including tumor cells. To switch into attack mode, they rely on chemical signals, and small amounts of reactive oxygen species (the group of molecules that includes free radicals) are among them.

Researchers at the University of Cambridge and Oregon Health & Science University examined the fluid surrounding cells inside tumors grown in mice. They found that the tumors create conditions that stop nearby T cells from activating. The key player is Peroxiredoxin 1 (PRDX1), a natural antioxidant protein. Cancer cells release large amounts of it, and it clears away the reactive oxygen species that T cells need. Without that signal, the T cells become less effective, so the tumor effectively builds a chemical shield.

What happened when the shield was removed

To test the idea, the team used CRISPR gene editing to create mouse cancer cells that could no longer make PRDX1. Immune cells became more active and tumor growth slowed. Some tumors that had resisted immunotherapy started to respond once the antioxidant defense was gone.

The researchers also looked for the same mechanism in people. They used three approaches: existing data on proteins released by human cancer cell lines, gene activity patterns across thousands of human tumors, and fluid collected from tumors surgically removed from patients. All three pointed the same way, suggesting that human cancers also release PRDX1 into their surroundings.

Why this matters for immunotherapy

Immunotherapies have transformed treatment for some patients, but many others get little or no benefit. This work offers one possible explanation: tumors that release PRDX1 may be suppressing the very T cells the treatment is meant to activate. As Professor Rahul Roychoudhuri put it, blocking this process made non-responding tumors start responding in the experiments, which makes the pathway worth pursuing as a drug target.

Dr. Robert Eil of Oregon Health & Science University suggests another direction: instead of antioxidants, pro-oxidants might help kick-start T cells against tumors.

A possible clue about antioxidant supplements

Large randomized trials of antioxidant supplements have not shown protection against cancer, and in some cases outcomes were worse. The new findings suggest one possible reason: removing too many reactive oxygen species could weaken the immune activation that helps fight tumors. The researchers stress that this does not prove supplements promote cancer. It shows how differently these molecules can behave in different biological settings.

What to keep in mind

  • The treatment effects were shown in mouse models. Evidence of the same mechanism in human cancers is supportive but not proof that blocking PRDX1 works in patients.
  • No PRDX1-targeting treatment has been shown to be safe or effective in people yet.
  • The authors advise that people with cancer should not change their diet, supplements or treatment based on these findings without speaking to a healthcare professional.

Sources