Cancer cells protect themselves from immune system attacks by releasing an antioxidant protein that neutralizes molecules necessary for T cell activation, according to a study published in the journal Science.
Researchers from Oregon Health & Science University and the University of Cambridge discovered that tumors release an antioxidant enzyme called peroxiredoxin 1 (PRDX1) into the tumor interstitium, the liquid surrounding cells within a tumor. This process creates an antioxidant-rich environment that removes reactive oxygen species (ROS), which T cells rely on for the signaling required to become fully activated and attack cancer cells.
A New “Redox Checkpoint”
While ROS—often called free radicals—have long been associated with genomic instability, DNA damage, and cancer-promoting signaling, the study reveals they are essential for the molecular signaling that switches on the cancer-killing functions of T cells. The researchers describe this mechanism as a previously unrecognized redox checkpoint
in antitumor immunity.
The research team found that cancer cells increase the expression of PRDX1 during immunoediting, an evolutionary process where tumors acquire characteristics to survive pressure from the immune system. Analyses of fluid from patient tumors, thousands of human tumors, and human cancer cell lines suggested this same mechanism may occur in people.
Impact on Immunotherapy
To test the role of PRDX1, researchers used CRISPR gene-editing technology to delete the protein from cancer cells. In multiple experimental models, the absence of tumor-derived PRDX1 increased antitumor immunity and enhanced immune activity. In one melanoma model, tumors lacking the protein were spontaneously rejected by the immune system.
Furthermore, eliminating PRDX1 made tumors that were previously resistant more responsive to immune checkpoint blockade, a form of immunotherapy. These findings suggest that blocking PRDX1 or restoring ROS signaling in T cells could be a strategy to overcome immunotherapy resistance.
While these possibilities remain preclinical, researchers are considering future therapeutic approaches, including drugs to neutralize tumor-derived antioxidants, therapies that block PRDX1 activity, or engineered immune cells designed to resist antioxidant-rich tumor environments.
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