Ilyas Sahin, Assistant Professor of Medicine at Harvard Medical School, Medical Oncologist at Massachusetts General Hospital, shared on X:
“Can tumors weaponize antioxidants?
A new Science study says yes.
T cells need a brief burst of reactive oxygen species to activate. Tumors exploit this dependency by releasing PRDX1, an antioxidant enzyme, into the surrounding fluid and erasing that signal.
Deleting PRDX1 from mouse tumors restored T-cell activity. Some tumors were rejected, while otherwise resistant melanomas became sensitive to checkpoint blockade (immunotherapy). Human data were supportive but limited.
A redox checkpoint hiding in plain sight. The findings may also provide biological context for a troubling clinical history:
- ATBC: beta-carotene increased lung cancer in smokers
- CARET: beta-carotene plus vitamin A led to 28% more lung cancers; stopped early
- SELECT: vitamin E increased prostate cancer by 17%
- Vitamin E during head and neck radiotherapy: less acute toxicity, but more recurrences or second primary cancers during supplementation.
The connection is not proven. This study examined tumor-derived PRDX1, not supplements, and most of the mechanistic evidence came from mice. Three of the four trials were prevention studies.
Still, redox biology is not a dial where more antioxidant is always better. High-dose supplements should not be assumed harmless during cancer care. So please discuss them with your oncology team.”
Title: Tumor-derived antioxidants suppress immunity by depriving T cells of reactive oxygen species
Authors: 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.
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