Tumor-derived antioxidants suppress immunity by depriving T cells of reactive oxygen species
- Alexander J. Wesolowski
- Ardon M. Pillay
- Panagiota Vardaka
- Rabab Nasrallah
- Randy Greaves
- Housaiyin Li
- Iliana Loffreda
- Chelsea Jenkin
- Andrew M. James
- Alica Nübling
- Christopher J. Ward
- Teresa von Linde
- Alberto G. Conti
- Sheue-Fen Tzeng
- Layla Dahmani
- Alexander C. Evans
- Sarah K. Whiteside
- Yumi Yamashita-Kanemaru
- Charlotte J. Imianowski
- Jie Yang
- Ignacio Moraga Gonzalez
- Jack Chapman
- Aws Al-deka
- Klaus Okkenhaug
- Michael P. Murphy
- Bartlomiej Swiatczak
- Geoffrey Guittard
- Enrico Lugli
- Lukas Flatz
- Ping-Chih Ho
- Robert L. Eil
- Rahul Roychoudhuri
2026-09-03
Reactive oxygen species (ROS) promote genomic instability and fuel oncogenic signaling in cancer, but antioxidant therapies have so far failed to improve, or worsen, cancer outcomes. Emerging data suggest that T cells depend on ROS for signal transduction. In this study, we show that tumors exploit this dependency, releasing antioxidant enzymes into the tumor environment to suppress T cell–mediated antitumor immunity. The interstitial fluid of tumors possesses potent antioxidant activity, associated with enrichment of the antioxidant enzyme peroxiredoxin 1 (PRDX1). Extracellular PRDX1 deprives T cells of ROS, preventing oxidative inactivation of phosphatases required for T cell receptor–driven kinase signaling and effector function. Prdx1 is up-regulated upon cancer immunoediting, and loss of PRDX1 within tumors enhances antitumor immunity and immunotherapy responses. These findings define a redox-dependent mechanism of tumor immunosuppression that is potentially amenable to therapeutic intervention.