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Updated: Jan 6, 2026

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
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NRF2 immunobiology in cancer: implications for immunotherapy and therapeutic targeting

Harit Panda1, Natalie G Rowland1, Caroline M Krall1

  • 1Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, USA.

Oncogene
|September 13, 2025
PubMed

Insights

Nuclear factor erythroid 2-related factor 2 (NRF2) is crucial for cellular defense but promotes cancer by hindering immune responses. Targeting NRF2 offers new therapeutic strategies for cancer treatment resistance and immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Nuclear factor erythroid 2-related factor 2 (NRF2) regulates cellular defense against oxidative stress and xenobiotics.
  • NRF2 controls over 200 genes impacting antioxidant response, drug metabolism, and resilience.
  • Constitutive NRF2 activation is frequent in cancer, influencing oncogenesis, immune evasion, and treatment resistance.

Purpose of the Study:

  • To comprehensively review NRF2's role in the tumor immune microenvironment.
  • To examine NRF2's impact on clinical outcomes and therapeutic opportunities.
  • To explore NRF2's association with anti-PD1 immunotherapy response.

Main Methods:

  • Review of genetically engineered mouse models.
  • Analysis of in vitro studies.
  • Examination of clinical trial samples.

Main Results:

  • NRF2 activation correlates with impaired anti-PD1 immunotherapy response across tumor types.
  • NRF2 promotes cancer cell resiliency and diminishes cytotoxic immune responses.
  • NRF2 drives metabolic reprogramming in cancer cells.

Conclusions:

  • NRF2 activity presents a therapeutic vulnerability in cancer.
  • Targeting NRF2 may overcome treatment resistance and enhance immunotherapy.
  • Developing combination strategies to target NRF2 dependencies is a promising future direction.

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