An international team of researchers from the University of Cambridge in the UK and Oregon Health & Science University (OHSU) in the US has uncovered the mechanism that allows malignant tumors to evade immune attacks. Tumor cells, it turns out, release natural antioxidants as a protective shield, paralyzing the body's defensive cells and their ability to fight the disease, infohub.kz reports.
The findings of the large-scale study were published in the journal Science. Tumor cells release the antioxidant PRDX1, depriving T lymphocytes of the reactive oxygen species they need to attack, and suppressing this shield strengthens immunotherapy, ScienceDaily writes.
For a long time, reactive oxygen species (ROS) and free radicals were seen solely as dangerous byproducts of cellular metabolism. However, biologists have found that cytotoxic T lymphocytes, which recognize and destroy abnormal cells, need small doses of ROS as a chemical signal to launch an attack. After studying the tumor microenvironment, the scientists discovered that cancer releases large amounts of the antioxidant protein peroxiredoxin-1 (PRDX1) into the intercellular fluid. This enzyme binds free radicals, stripping immune cells of their trigger mechanism.
In experiments on mice, the scientists switched off PRDX1 production using CRISPR gene editing, which restored T lymphocyte activity and slowed tumor growth. In addition, treatment-resistant tumors became sensitive to immunotherapy once again. An analysis of genetic databases and patient biopsies confirmed that a similar process occurs in the human body.
One of the lead authors of the study, Dr. Xan Wesolowski, stressed that the research changes the conventional view of the physiological role of radicals. Professor Rahul Roychoudhuri noted that removing the antioxidant shield will make it possible to overcome drug resistance in tumors, while Dr. Robert Eil pointed to the promise of using pro-oxidant substances to activate lymphocytes. The discovery also explained why taking antioxidant supplements does not prevent cancer in clinical trials.