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Updated: Oct 27, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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Optineurin Guards IFNγ Signaling in Cancer Cells

Camilla Salvagno1,2, Juan R Cubillos-Ruiz1,2,3

  • 1Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York. jur2016@med.cornell.edu cas4005@med.cornell.edu.

Cancer Discovery
|July 21, 2021
PubMed

Insights

Optineurin stabilizes the interferon-gamma receptor (IFNGR1) in cancer cells. Its loss impairs immune signaling and allows tumors to evade immune detection.

Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • Interferon-gamma (IFNγ) signaling is crucial for anti-tumor immunity.
  • The stability of the IFNγ receptor (IFNGR1) is critical for effective signaling.
  • Mechanisms regulating IFNGR1 stability in cancer remain incompletely understood.

Purpose of the Study:

  • To investigate the role of optineurin in regulating IFNGR1 stability in malignant cells.
  • To determine the functional consequences of optineurin loss on IFNγ signaling and immune evasion in colorectal cancer.

Main Methods:

  • Utilized colorectal cancer cell lines with varying optineurin expression.
  • Assessed IFNGR1 protein levels and degradation pathways.
  • Measured IFNγ-induced signaling, MHC-I expression, and immune cell interactions.

Main Results:

  • Optineurin was identified as a key regulator of IFNGR1 stability.
  • Loss of optineurin led to increased IFNGR1 degradation.
  • Impaired IFNγ signaling and reduced MHC-I expression were observed in optineurin-deficient cells.
  • Optineurin deficiency enhanced the ability of colorectal cancer cells to evade adaptive immune control.

Conclusions:

  • Optineurin plays a critical role in maintaining IFNGR1 stability in colorectal cancer.
  • Optineurin loss promotes tumor immune evasion by disrupting IFNγ signaling and MHC-I expression.
  • Targeting optineurin could represent a novel strategy to enhance anti-tumor immunity.

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