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

Abstract

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 TNFR2⁺CD4⁺ T cells were Foxp3^-CD25^-. However, the percentage of TNFR2⁺ cells was significantly higher in Foxp3⁺CD25⁺CD4⁺ Tregs compared to Foxp3^-CD25^-CD4⁺, Foxp3⁺CD25^-CD4⁺, and Foxp3^-CD25⁺CD4⁺ T cell subsets. Among these subsets, Foxp3⁺CD25⁺TNFR2⁺CD4⁺ T cells were found to have the highest intensity of TNFR2 expression. The intensity of Foxp3 expression in Foxp3⁺CD25⁺TNFR2⁺CD4⁺ Treg cells was significantly higher than in their TNFR2^- counterpart. Collectively, we showed that most of TNFR2⁺CD4⁺ T lymphocytes were Foxp3^-CD25^-, while the majority of Foxp3⁺CD25⁺CD4⁺ 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.

Keywords: Breast cancer; Regulatory T cells; TNFR2; Tumor-draining lymph nodes.