The expression pattern of membranous TNF-α is distinct from its intracellular form in breast cancer-draining lymph...

Tumor necrosis factor-alpha (TNF-α) is mostly known as a soluble cytokine. This study, however, focused on its membranous form whose significance is rarely investigated in antitumor immunity. Herein, we assessed the expression of both membranous and intracellular forms of TNF-α (m/icTNF-α) in the lymphocytes derived from breast cancer-draining lymph nodes. CD4⁺T cells were the main subset expressing mTNF-α with the highest intensity, whereas icTNF-α expression was most intense in CD8⁺T cells. An inverse correlation was seen between the frequency of mTNF-α and the expression intensity of this cytokine in B cells. In the clinical context, the higher intensity of mTNF-α expression in CD19⁺ cells correlated with poor prognosticators, while the frequency of mTNF-α⁺CD19⁺ cells showed a reverse correlation with the number of involved lymph nodes. The two forms of TNF-α did not show similar associations with cancer parameters, which highlights the complex role of this cytokine in breast cancer immunity.