Increased prevalence of tumor-infiltrating regulatory T cells is closely related to their lower sensitivity to H2O2-induced apoptosis in gastric and esophageal cancer

Purpose and experimental design

Although an increase in regulatory T cells (Tregs) is observed in tumor microenvironments, the underlying mechanism is not fully clarified. Since it was suggested that Tregs showed a lower sensitivity toward oxidative stress in comparison with conventional T cells, in the present study, we investigated the H₂O₂ production and apoptosis of Tregs in gastric and esophageal cancer tissues, employing flow cytometric analysis using fresh samples (n = 93) and immunohistochemical analysis (n = 203).

Results

The increased tumor-infiltrating Tregs coexisted with elevated H₂O₂ production according to disease progression. The grade of apoptosis in Tregs was less pronounced than that in conventional T cells, and there was a positive correlation between H₂O₂ production and the grade of apoptosis in conventional T cells, while there was no correlation between H₂O₂ production and the grade of apoptosis in Tregs. Moreover, Tregs were less sensitive to H₂O₂-induced apoptosis compared with conventional T cells in vitro.

Conclusions

We have demonstrated that the increased prevalence of tumor-infiltrating Tregs closely related to their lower sensitivity to H₂O₂-induced apoptosis.