Tumors release antioxidants to disarm T cells, study finds

Tumors have a new trick up their sleeve — and it involves turning the body's own antioxidant defenses against the immune system. A study published Thursday in the journal Science reveals that cancer cells release an antioxidant protein called peroxiredoxin-1, or PRDX1, to strip away the reactive oxygen species that T cells need to activate and kill tumors.news.ohsu+1

The research, led by teams at the University of Cambridge and Oregon Health & Science University, identifies what scientists are calling a "redox checkpoint" — a previously unrecognized mechanism by which tumors manipulate their chemical environment to evade immune destruction.science+1

How Tumors Smother the Immune Response

Reactive oxygen species, commonly known as free radicals, have long been considered harmful byproducts of metabolism. But the new findings upend that assumption in the context of cancer immunity. By analyzing the fluid surrounding tumor cells in mice, researchers discovered that cancers flood their microenvironment with PRDX1, effectively mopping up the small amounts of ROS that T cells require to switch on their killing ability.medicalxpress+1

"We tend to think of reactive oxygen species purely as damaging byproducts of metabolism. But we are increasingly understanding they have important functions within cells, and T cells need them to activate," said Alexander Wesolowski, first author of the study and a researcher at the University of Cambridge. "Our study develops this picture, revealing that tumours can exploit this very dependency to evade elimination."cam

Using CRISPR gene-editing technology, the team created cancer cells unable to produce PRDX1. The results were striking: in one melanoma model, tumors lacking the protein were spontaneously rejected by the immune system. In others, eliminating PRDX1 made previously resistant tumors responsive to immune checkpoint blockade, a common form of immunotherapy.news.ohsu+1

Implications for Immunotherapy and Antioxidant Use

The researchers confirmed the mechanism extends to human cancers. Across analyses of human cancer cell lines, gene activity data from thousands of tumors, and fluid collected from patient tumors, they found consistent evidence that human cancers release PRDX1 into their surroundings.medicalxpress+1

"We've found a new way by which cancers shut down the immune system. When we block this process, tumours that don't respond to some immunotherapies start responding to treatment," said Rahul Roychoudhuri, a professor at Cambridge's Department of Pathology.cam

The findings may also shed light on a long-standing puzzle: why antioxidant supplements have failed to reduce cancer risk in large clinical trials and in some cases worsened outcomes. The discovery that T cells depend on ROS to fight tumors suggests antioxidants could inadvertently blunt the immune system's cancer-fighting ability. The team cautioned that people living with cancer should not change their treatment or diet without medical advice.medicalxpress+1

A New Target for Future Therapies

Potential therapeutic approaches include drugs that neutralize tumor-derived antioxidants, therapies that block PRDX1 activity, and engineered immune cells resistant to antioxidant-rich tumor environments. Robert Eil, associate professor of surgery at OHSU and co-senior author, noted the work opens an entirely new pathway for drug development, though translating the findings into treatments will take time.news.ohsu

"Every time we uncover a new way tumors suppress the immune system, we gain another opportunity to fight back," Eil said. "That's how better treatments are built."news.ohsu