Expression data of human Tregs treated with TNFR2 agonist antibody. Expression data of human Tregs treated with TNFR2 agonist antibody

Tumor necrosis factor receptor 2 (TNFR2), a membrane-bound tumor necrosis factor receptor expressed by regulatory T cells (Tregs), participates in Treg proliferation. Although a specific TNFR2 pathway has been reported, the signaling mechanism has not been completely elucidated. This study sought to clarify TNFR2 signaling in human Tregs using amplicon sequencing and single-cell RNA-sequencing to assess Tregs treated with a TNFR2 agonist antibody. Pathway enrichment analysis based on differentially expressed genes highlighted tumor necrosis factor α signaling via nuclear factor-kappa B, interleukin-2 signal transducer and activator of transcription 5 signaling, interferon-γ response, and cell proliferation-related pathways in Tregs after TNFR2 activation. TNFR2-high Treg-focused analysis found that these pathways were fully activated in cancer Tregs, showing high TNFR2 expression. Collectively, these findings suggest that TNFR2 orchestrates multiple pathways in cancer Tregs, which could help cancer cells escape immune surveillance, making TNFR2 signaling a potential anticancer therapy target. Overall design: Examination of gene expression profile in Treg treated with TNFR2 agonist antibody.