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Updated: Oct 7, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
TNFR2 pathways are fully active in cancer regulatory T cells
Yuumi Okuzono1, Yo Muraki1, Shuji Sato1
1Immunology Unit, Research, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa 251-8555, Japan.
Abstract:
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.
Insights
Tumor necrosis factor receptor 2 (TNFR2) signaling in regulatory T cells (Tregs) activates multiple pathways. This TNFR2 activation in cancer Tregs may help tumors evade immune surveillance, suggesting TNFR2 as an anticancer therapy target.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- Tumor necrosis factor receptor 2 (TNFR2) is expressed by regulatory T cells (Tregs) and influences their proliferation.
- The precise signaling mechanisms of TNFR2 in human Tregs remain incompletely understood.
Purpose of the Study:
- To elucidate the signaling pathways regulated by TNFR2 in human Tregs.
- To investigate the role of TNFR2 signaling in cancer-associated Tregs.
Main Methods:
- Utilized amplicon sequencing and single-cell RNA sequencing on human Tregs stimulated with a TNFR2 agonist antibody.
- Performed pathway enrichment analysis on differentially expressed genes.
Main Results:
- TNFR2 activation in Tregs upregulated pathways including TNFα signaling via NF-κB, IL-2/STAT5 signaling, and interferon-γ response.
- These pathways were found to be fully activated in TNFR2-high cancer Tregs.
- TNFR2 signaling orchestrates multiple pathways in cancer Tregs, potentially aiding immune evasion.
Conclusions:
- TNFR2 signaling plays a significant role in the function of cancer Tregs.
- Targeting TNFR2 signaling represents a potential therapeutic strategy for anticancer treatments.
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