Regulatory T cells express Tumor Necrosis Factor Receptor 2 with the highest intensity among CD4 T cells in the draining lymph nodes of breast cancer.

Tumor Necrosis Factor Receptor 2 (TNFR2) is one of the receptors of TNF-α, which is expressed on various cell types. TNFR2 signaling has a balancing role between regulatory and effector functions of T cells. Herein, we investigated the expression of TNFR2 on regulatory T cells (Tregs) and non-Tregs in breast tumor-draining lymph nodes. Mononuclear cells were isolated from 16 axillary lymph nodes, and the expressions of TNFR2, Foxp3 and CD25 were assessed in CD4 T cells by flow cytometry. Our results showed that the majority of TNFR2CD4 T cells were Foxp3CD25. However, the percentage of TNFR2 cells was significantly higher in Foxp3CD25CD4 Tregs compared to Foxp3CD25CD4, Foxp3CD25CD4, and Foxp3CD25CD4 T cell subsets. Among these subsets, Foxp3CD25TNFR2CD4 T cells were found to have the highest intensity of TNFR2 expression. The intensity of Foxp3 expression in Foxp3CD25TNFR2CD4 Treg cells was significantly higher than in their TNFR2 counterpart. Collectively, we showed that most of TNFR2CD4 T lymphocytes were Foxp3CD25, while the majority of Foxp3CD25CD4 Tregs were TNFR2, and they expressed TNFR2 with the highest intensity. This report highlights the importance of TNFR2 expression on Tregs and paves the way for further investigation of the effects of TNF-α on the suppressive activity of Tregs in the tumor microenvironment.