Naturally occurring regulatory T cells show reduced sensitivity toward oxidative stress–induced cell death

Although the authors of several studies report elevated numbers of immunosuppressive regulatory T cells (Tregs) in hematologic and solid malignancies, the underlying mechanism is not fully clarified. Cancer is associated with oxidative stress mediated through reactive oxygen species produced by malignant cells, granulocytes, tumor-associated macrophages, and myeloid-derived suppressor cells. Oxidative stress is known to have detrimental effects on natural killer (NK) and T cells during chronic inflammatory conditions and cancer. Paradoxically, greater numbers of Tregs can be detected at tumor sites, indicating that Tregs can persist in this environment of increased oxidative stress. We demonstrate that Tregs, especially naive CD45RA(+), exhibit reduced sensitivity to oxidative stress-induced cell death and maintain their suppressive function, a phenomenon that may be attributed to their observed high antioxidative capacity. This newly described characteristic could explain their enrichment in malignancies associated with increased levels of oxidative stress.