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Updated: Apr 3, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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The Nuclear Orphan Receptor NR2F6 Is a Central Checkpoint for Cancer Immune Surveillance

Natascha Hermann-Kleiter1, Victoria Klepsch1, Stephanie Wallner2

  • 1Translational Cell Genetics, Department for Pharmacology and Genetics, Medical University of Innsbruck, 6020 Innsbruck, Austria.

Cell Reports
|September 22, 2015
PubMed

Insights

Genetic ablation of nuclear receptor subfamily 2, group F, member 6 (NR2F6) enhances prostate cancer survival and anti-tumor immunity. NR2F6 deficiency in T cells boosts immune responses, improving cancer rejection and memory.

Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • Nuclear receptor subfamily 2, group F, member 6 (NR2F6) is an orphan nuclear receptor.
  • Prostate cancer progression is often linked to immune evasion.

Purpose of the Study:

  • To investigate the role of NR2F6 in prostate cancer immunity.
  • To determine if NR2F6 acts as a target for enhancing anti-tumor immune responses.

Main Methods:

  • Utilized the TRAMP mouse model for prostate cancer.
  • Generated and analyzed Nr2f6 knockout mice (Nr2f6(-/-)).
  • Assessed T cell populations, cytokine expression, and tumor rejection following NR2F6 genetic ablation.

Main Results:

  • Nr2f6 deficiency significantly improved survival in the TRAMP model.
  • Nr2f6(-/-) mice rejected tumors and developed immunological memory.
  • Increased CD4(+) and CD8(+) T cell frequencies and enhanced IL-2/IFN-γ expression were observed at the tumor site.
  • NR2F6 directly represses NFAT/AP-1 activity on IL-2 and IFN-γ promoters in T cells.
  • Adoptive transfer of Nr2f6-deficient T cells delayed tumor growth.

Conclusions:

  • NR2F6 functions as an intracellular immune checkpoint in effector T cells.
  • Targeting NR2F6 can enhance anti-cancer immunity and improve therapeutic outcomes.

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