Scientists have discovered that cancer can hijack the antioxidant protein Peroxiredoxin 1 (PRDX1) to disarm immune cells, revealing a previously unknown way tumors evade the body's defenses. The finding, published in Science, could lead to new strategies for making immunotherapies more effective, especially in patients whose tumors resist existing treatments.
Researchers at the University of Cambridge and Oregon Health & Science University found that a naturally occurring antioxidant protein called Peroxiredoxin 1 (PRDX1) helps cancer cells escape attack from T cells, among the immune system’s most important defenses.
T cells need small amounts of reactive oxygen species, molecules that include free radicals, to switch into attack mode and destroy tumor cells. The study shows that cancer cells release large quantities of PRDX1 into their surroundings, where it mops up the reactive oxygen species that T cells depend on. Without those activating signals, the immune cells become less effective.
“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 Dr. Xan Wesolowski, a lead author from Cambridge's Department of Pathology. “Our study develops this picture, revealing that tumors can exploit this very dependency to evade elimination.”
Using CRISPR gene editing to modify cancer cells in mice so they could no longer produce PRDX1, the team found that immune cells became more active and tumor growth was reduced. Further evidence from human cancer cell lines, gene activity in thousands of tumors, and fluid from surgically removed tumors supported the conclusion that human cancers also release PRDX1 into their surroundings.
The research points to a new target for cancer immunotherapy. In experimental models, some tumors that had resisted treatment became responsive when the antioxidant defense was blocked.
“We’ve found a new way by which cancers shut down the immune system,” said Professor Rahul Roychoudhuri, also from Cambridge’s Department of Pathology. “When we block this process, tumors that don’t respond to some immunotherapies start responding to treatment. That tells us this is a pathway worth targeting therapeutically, and there are several ways we might be able to achieve this.”
Dr. Robert Eil from Oregon Health & Science University suggested a different chemical approach: “Our study suggests a possible way to boost T cell immunotherapies. Rather than using antioxidants, it could be that pro oxidants can kickstart the T cells into action against tumor cells.”
The results may also help explain why some large clinical trials of antioxidant supplements have failed to show cancer protection, and why antioxidant supplementation has in some cases been associated with worse outcomes. While reactive oxygen species can damage cells, they also help activate immune defenses. Removing too many of them might inadvertently weaken the immune system’s ability to fight cancer.
The researchers stress that the findings are preclinical and that potential treatment strategies have not yet been established as safe or effective in patients. People living with cancer should not change their diet, supplement use, or medical treatment based on these results without consulting a healthcare professional.
Analysis
Why This Matters
- The discovery identifies a new mechanism by which tumors evade the immune system, potentially explaining why some patients fail to respond to immunotherapy
- Blocking the antioxidant shield could make existing immunotherapies effective for more patients, including those with currently resistant tumors
- The findings challenge the simple view of antioxidants as universally protective, with possible implications for supplement use during cancer treatment
Background
The study was published in the journal Science and conducted by researchers at the University of Cambridge and Oregon Health & Science University. It was supported by the Medical Research Council, the European Research Council, Wellcome, and the National Institutes of Health/National Cancer Institute. The research used mouse models, human cancer cell lines, data from thousands of human tumors, and fluid from surgically removed tumors.
Key Perspectives
- Dr. Xan Wesolowski (University of Cambridge): “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.”
- Professor Rahul Roychoudhuri (University of Cambridge): “We’ve found a new way by which cancers shut down the immune system. When we block this process, tumors that don’t respond to some immunotherapies start responding to treatment. That tells us this is a pathway worth targeting therapeutically.”
- Dr. Robert Eil (Oregon Health & Science University): “Our study suggests a possible way to boost T cell immunotherapies. Rather than using antioxidants, it could be that pro oxidants can kickstart the T cells into action against tumor cells.”
What to Watch
- Clinical trials testing inhibitors of PRDX1 or other strategies to block the antioxidant shield in cancer patients
- Studies examining whether pro-oxidant agents can safely enhance T cell activity in human tumors
- Further research into the role of antioxidant supplements in cancer progression and treatment outcomes
Checked
12 claims in this story checked against 1 source: 12 supported.
Show each claim
- SupportedThe headline says cancer uses an antioxidant shield to disable immune cells.Latest Science News -- ScienceDaily: “tumors appear to exploit this requirement by releasing natural antioxidants that interfere with the immune system's ability to fight back.”
- SupportedThe summary says tumors release PRDX1 to weaken T cells, suggesting a way to improve immunotherapy.Latest Science News -- ScienceDaily: “Cancer cells release large quantities of this protein into their surroundings, where it removes the reactive oxygen species that T cells need to function. Without those activating signals, the immune cells become less effective at destroying cancer.”
- SupportedXan Wesolowski said: “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,”Latest Science News -- ScienceDaily: “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.”
- SupportedXan Wesolowski continued: “Our study develops this picture, revealing that tumors can exploit this very dependency to evade elimination.”Latest Science News -- ScienceDaily: “Our study develops this picture, revealing that tumors can exploit this very dependency to evade elimination.”
- SupportedXan Wesolowski is identified as a lead author from Cambridge's Department of Pathology.Latest Science News -- ScienceDaily: “Dr. Xan Wesolowski, one of the lead authors from the University of Cambridge's Department of Pathology”
- SupportedRahul Roychoudhuri said: “We’ve found a new way by which cancers shut down the immune system. When we block this process, tumors that don’t respond to some immunotherapies start responding to treatment. That tells us this is a pathway worth targeting therapeutically, and there are several ways we might be able to achieve this.”Latest Science News -- ScienceDaily: “We've found a new way by which cancers shut down the immune system. When we block this process, tumors that don't respond to some immunotherapies start responding to treatment. That tells us this is a pathway worth targeting therapeutically, and there are several ways we might be able to achieve this.”
- SupportedRobert Eil said: “Our study suggests a possible way to boost T cell immunotherapies. Rather than using antioxidants, it could be that pro oxidants can kickstart the T cells into action against tumor cells.”Latest Science News -- ScienceDaily: “Our study suggests a possible way to boost T cell immunotherapies. Rather than using antioxidants, it could be that pro oxidants can kickstart the T cells into action against tumor cells.”
- SupportedIn mice, CRISPR-modified cancer cells that could no longer produce PRDX1 were associated with more active immune cells and reduced tumor growth.Latest Science News -- ScienceDaily: “Without PRDX1, immune cells became more active, and tumor growth was reduced.”
- SupportedEvidence from human cancer cell lines, gene activity in thousands of tumors, and fluid from surgically removed tumors supported that human cancers release PRDX1 into their surroundings.Latest Science News -- ScienceDaily: “They examined 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 lines of evidence supported the same conclusion. Human cancers also release PRDX1 into the surrounding environment”
- SupportedSome tumors that had resisted immunotherapy became responsive when the antioxidant defense was disrupted in experimental models.Latest Science News -- ScienceDaily: “Some tumors that had previously resisted treatment became responsive when the antioxidant defense was disrupted.”
- SupportedThe findings may help explain why some large clinical trials of antioxidant supplements did not demonstrate cancer protection and why supplementation has sometimes been associated with worse outcomes.Latest Science News -- ScienceDaily: “several large randomized clinical trials have failed to demonstrate such protection. In some cases, antioxidant supplementation has even been associated with worse outcomes.”
- SupportedThe findings are preclinical, and potential treatment strategies have not been established as safe or effective in patients.Latest Science News -- ScienceDaily: “The researchers also emphasize that their experimental findings remain preclinical. Although they identified evidence of the same antioxidant mechanism in human cancers, the potential treatment strategies have not yet been established as safe or effective in patients.”
