Cancer Cells Release Antioxidants to Prevent Immune Cells From Destroying Them

Cancer cells may evade the immune system by creating an antioxidant-rich environment that chemically suppresses T cells, according to research by teams at the University of Cambridge and Oregon Health & Science University.

The study focuses on reactive oxygen species, or ROS, often associated with aging, DNA damage and cancer. Researchers found that cancer-fighting T cells also need small amounts of ROS to activate and begin their destructive response. Tumors release large quantities of peroxiredoxin 1, or PRDX1, a natural antioxidant protein that removes those signals from the surrounding environment.

To test whether PRDX1 directly contributes to immune evasion, the researchers used CRISPR gene editing to create mouse cancer cells unable to produce the protein. Immune-cell activity increased, and tumor growth was restricted across several experimental models.

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Surprising that antioxidants are not always beneficial in the context of cancer.

The team then looked for the same mechanism in humans. It examined proteins released by human cancer cell lines, analyzed gene activity in thousands of human tumors and studied fluid surrounding tumors removed from patients. All three approaches produced evidence that human cancers also release PRDX1 into their surroundings, where it can eliminate the ROS on which T cells depend.

Robert Eil of Oregon Health & Science University called it “surprising that antioxidants are not always beneficial in the context of cancer.” He cautioned that the findings do not mean patients will have a drug tomorrow, but said they open a new area for exploration. The researchers said the discovery may be especially relevant because many cancers do not respond to immunotherapy or later develop resistance to it.

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This does not mean that tomorrow patients will have a drug available, but it opens a completely new path to explore. The discovery of new targets is the starting point for future treatments.