Tumors release an antioxidant protein that switches off the immune cells built to kill them
Cambridge researchers find cancers flood their surroundings with the antioxidant PRDX1 to disarm T cells. Blocking it in mice boosted immunity and immunotherapy.
Summary
Cancer immunology gets a surprising twist: tumors use antioxidants as a shield against the immune system. Researchers at the University of Cambridge and Oregon Health & Science University found that T cells, the immune cells that destroy cancer, need small amounts of reactive oxygen species (a group of molecules that includes free radicals) to switch into attack mode. Tumors release large amounts of an antioxidant protein called Peroxiredoxin 1 (PRDX1), which mops up those signaling molecules and leaves nearby T cells unable to activate. When the team used CRISPR to stop mouse tumors from making PRDX1, immune cells became more active and tumors grew more slowly. Blocking the mechanism also improved responses to immunotherapy in mice. Data from human cancer cell lines, thousands of human tumors and fluid from surgically removed tumors suggest people's cancers may use the same strategy. The work, published in Science, is early and preclinical, but it points to a new way to help immunotherapy work in patients whose tumors resist it.
Detailed Summary
Antioxidants have long been seen as protective molecules, and free radicals as cellular villains. New research published in Science complicates that picture and reveals a previously unknown way that cancer evades the immune system.
Researchers at the University of Cambridge and Oregon Health & Science University found that T cells, the immune cells that recognize and destroy tumor cells, depend on small amounts of reactive oxygen species, a group of molecules that includes free radicals. These molecules act as activating signals that help T cells switch into attack mode. Tumors, it turns out, exploit this requirement.
By analyzing the fluid surrounding cells inside mouse tumors, the team identified a naturally occurring antioxidant protein, Peroxiredoxin 1 (PRDX1), that cancer cells release in large quantities. PRDX1 strips away the reactive oxygen species that T cells need, so nearby T cells cannot activate properly. In effect, the tumor builds a chemical shield around itself.
To test this, the scientists used CRISPR gene editing to create cancer cells that could not make PRDX1. In mice, these tumors grew more slowly and immune cells within them were more active. Blocking the mechanism also improved responses to immunotherapy. The researchers then checked human data, including proteins released by human cancer cell lines, gene activity patterns across thousands of human tumors, and fluid from tumors removed from patients, and found evidence that human cancers may use the same strategy.
The practical implication is a potential new drug target: inhibiting PRDX1 or its effects could make immunotherapy work in patients whose tumors currently resist treatment. It also suggests that the relationship between antioxidants and cancer is more nuanced than commonly assumed.
Important caveats apply. The core experiments were done in mice, and no PRDX1-blocking therapy has been tested in people. This work does not show that dietary antioxidants or supplements promote cancer, since the antioxidant here is a protein secreted by tumors in their local environment. Readers should not change supplement use based on this finding, and should look to the full paper and future clinical trials for confirmation.
Key Findings
- T cells need small amounts of reactive oxygen species to activate and destroy cancer cells.
- Tumors release large amounts of the antioxidant protein PRDX1, which removes those activating signals.
- CRISPR deletion of PRDX1 in mouse tumors increased immune activity and slowed tumor growth.
- Blocking this mechanism improved immunotherapy responses in mice.
- Human tumor data suggest the same PRDX1 strategy may operate in people's cancers.
Methodology
This is a news report summarizing a peer-reviewed study in Science, distributed by ScienceDaily from a University of Cambridge release. The evidence combines mouse tumor experiments with CRISPR editing and analyses of human cell line, tumor gene expression and patient tumor fluid data.
Study Limitations
Key causal evidence comes from mice, and the human data are largely correlative, so benefit in patients is unproven. The article excerpt is truncated and gives no effect sizes, cancer types or safety considerations for blocking PRDX1. Check the original Science paper for details.
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