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.

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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