Systemic Immune Remodeling in Breast Cancer: Selective Enrichment of TNFR2

Purpose: Tumor necrosis factor-alpha (TNF-α) exerts both tumor-promoting and tumor-suppressive effects in breast cancer through its two molecular forms, transmembrane (tmTNF-α) and soluble (sTNF-α), which signal via distinct receptors, TNFR1 and TNFR2. While TNFR1 is minimally expressed on lymphocytes within tumor-draining lymph nodes, TNFR2 predominates on B and T cells, highlighting its key role in immune regulation. Considering that cancer affects systemic immunity, this study assessed TNFR2 expression on circulating lymphocytes in breast cancer patients to elucidate immune alterations across disease stages. Patients and Methods: Peripheral blood was collected from 50 women with histologically confirmed breast cancer and 24 age-matched healthy volunteers. Lymphocytes were isolated using density gradient centrifugation, and TNFR2 expression on B and T cell subsets was evaluated by flow cytometry with specific monoclonal antibodies. Results: Patients exhibited marked lymphopenia, with significantly reduced frequencies of CD19 Conclusion: Elevated TNFR2 expression on peripheral lymphocytes, despite overall lymphocyte depletion, underscores its potential as a biomarker and immunomodulatory target in breast cancer progression.